madman
Super Moderator
About Androderm® (testosterone transdermal system) | Learn About the Androderm Patch®
Learn more about the Androderm® patch, including usage and spreading testosterone. View Important Risk Information and full Prescribing Information on the website.
ANDRODERM® (testosterone transdermal system) is designed to deliver testosterone continuously for 24 hours following application to intact, non-scrotal skin (e.g., back, abdomen, thighs, upper arms).
Four strengths of ANDRODERM® are available that deliver approximately 2 mg, 2.5 mg, 4 mg, or 5 mg of testosterone per day. ANDRODERM® has a central drug delivery reservoir surrounded by a peripheral adhesive area.
The ANDRODERM® 2 mg/day system has a total contact surface area of 32 cm 2 with a 6.0 cm 2 central drug delivery reservoir containing 9.7 mg testosterone USP, dissolved in an alcohol-based gel. The ANDRODERM® 2.5 mg/day system has a total contact surface area of 37 cm 2 with a 7.5 cm 2 central drug delivery reservoir containing 12.2 mg testosterone USP, dissolved in an alcohol-based gel. The ANDRODERM® 4 mg/day system has a total contact surface area of 39 cm 2 with a 12.0 cm 2 central drug delivery reservoir containing 19.5 mg testosterone USP, dissolved in an alcohol-based gel. The ANDRODERM® 5 mg/day system has a total contact surface area of 44 cm 2 with a 15 cm 2 central drug delivery reservoir containing 24.3 mg testosterone USP, dissolved in an alcohol-based gel. Testosterone USP is a white, or creamy white crystalline powder or crystals chemically described as 17ßhydroxyandrost-4-en-3-one.
The ANDRODERM® systems have six components as shown in Figure 1. Proceeding from the top toward the surface attached to the skin, the system is composed of (1) metalized polyester (ethylene-methacrylic acid copolymer)/ethylene vinyl acetate backing film with alcohol-resistant ink, (2) a drug reservoir of testosterone USP, alcohol USP, glycerin USP, glycerol monooleate, methyl laurate, sodium hydroxide NF, to adjust pH, and purified water USP, gelled with carbomer copolymer Type B NF, (3) a permeable polyethylene microporous membrane, and (4) a peripheral layer of acrylic adhesive surrounding the central, active drug delivery area of the system. Prior to the opening of the system and application to the skin, the central delivery surface of the system is sealed with a peelable laminate disc (5) composed of a five-layer laminate containing polyester/polyesterurethane adhesive/aluminum foil/polyester-urethane adhesive/polyethylene. The disc is attached to and removed with the release liner (6), a silicone-coated polyester film, which is removed before the system can be used.
The active ingredient in the system is testosterone. The remaining components of the system are pharmacologically inactive.
12.3 Pharmacokinetics Absorption
ANDRODERM® delivers physiologic amounts of testosterone, producing circulating testosterone concentrations that approximate the normal concentration range (300 – 1030 ng/dL) seen in healthy men. ANDRODERM® provides a continuous daily dose of testosterone in a self-contained transdermal system. Following ANDRODERM® application, testosterone is continuously absorbed during the 24-hour dosing period with a median (range) Tmax of 8 (4-12) hours.
In a group of 34 hypogonadal men, application of two ANDRODERM® 2.5 mg/day systems to the abdomen, back, thighs, or upper arms resulted in average testosterone absorption of 4 to 5 mg, over 24 hours. The serum testosterone concentration profiles during application were similar for these sites (Table 3). Applications to the chest and shins resulted in greater interindividual variability and average 24-hour absorption of 3 to 4 mg.
Table 3: Mean serum testosterone concentrations (ng/dL) measured during single-dose applications of two ANDRODERM® 2.5 mg/day systems applied at night to different sites in 34 hypogonadal men
In a steady-state study of 12 hypogonadal men, nightly application of 1, 2, or 3 ANDRODERM® 2.5 mg/day systems resulted in increases in the mean morning serum testosterone concentrations. These concentrations averaged 424 ng/dL, 584 ng/dL, and 766 ng/dL with the application of 1, 2, and 3 systems, respectively. The mean baseline serum testosterone concentration was 76 ng/dL.
In a study of 20 hypogonadal patients, two ANDRODERM® 2.5 mg/day systems and a single ANDRODERM® 5 mg/day system produced equivalent serum testosterone concentration profiles. Average steady-state concentrations over 24 hours (Cssavg) were 613 ± 169 ng/dL and 621 ± 176 ng/dL for the two 2.5 mg/day and single 5 mg/day systems, respectively. Cmax values were 925 ± 340 ng/dL for the two 2.5 mg/day systems and 905 ± 254 ng/dL for the single 5 mg/day system.
14 CLINICAL STUDIES
ANDRODERM® 2 mg/day and 4 mg/day were studied in a trial designed to evaluate the use and titration of 2 mg/day and 4 mg/day systems in a clinic setting of 40 men with hypogonadism. Thirty-eight of the 40 subjects (95%) who were enrolled in the study were white and 2 subjects were African American. Ten (25%) subjects were Hispanic and 30 (75%) were Non-Hispanic. Men were between 34 and 76 years of age (mean: 55 years). Patients had previously been on stable therapy of ANDRODERM® 5 mg; Androgel® 2.5 g, 5 g, 7.5 g or 10 g; or Testim® 2.5 g or 5 g daily before switching to ANDRODERM® 4 mg/day.
Patients applied an ANDRODERM® 4 mg/day system around 10 p.m. once daily for 14 days and then were titrated up to 6 mg/day or down to 2 mg/day according to a morning serum testosterone concentration obtained at 6 a.m. on Day 8. Out of 36 patients who entered the study, 31 (86%) patients remained on the 4 mg/day dose, 4 (11%) were titrated downward to 2 mg/day and 1 (3%) was titrated upward to 6 mg/day based on the Day 8 testosterone concentrations. The one patient that was titrated to 6 mg/day was discontinued from the study for a non-safety-related reason. Of the patients who were receiving ANDRODERM® 5 mg/day prior to study entry (n = 11), 10 remained at 4 mg/day after titration, and 1 was titrated down to the 2 mg/day dose.
After a total of 28 days of therapy, 34 of the 35 subjects (97%) had serum testosterone Cavg within the normal range during the dosing period, with the lower bound of the 95% confidence interval for this estimate is 85% (Table 4). One subject who received ANDRODERM® 4 mg/day treatment had serum testosterone Cavg below 300 ng/dL and none had Cavg concentrations above 1030 ng/dL. The mean (SD) serum testosterone Cmax following treatment with the 2 mg/day (N = 4) and 4 mg/day (N = 31) systems was 648 (145) ng/dL and 696 (158) ng/dL, respectively. Table 4 summarizes testosterone Cavg categories by treatment.
Figure 2 summarizes the pharmacokinetic profiles of total testosterone in 35 patients completing 28 days of ANDRODERM® treatment applied as a starting dose of 4 mg/day for the initial 14 days followed by a possible dose titration.
Figure 2. Mean (SD) Steady-State Serum Total Testosterone Concentration (ng/dL) on Day 28
In separate clinical studies using the ANDRODERM® 2.5 mg/day system, 1% used 2.5 mg daily, 93% of patients used 5 mg daily, and 6% used 7.5 mg daily. The hormonal effects of the ANDRODERM® 2.5 mg/day system as a treatment for male hypogonadism were demonstrated in four open-label trials that included 94 hypogonadal men, ages 15 to 65 years. In these trials, ANDRODERM® produced average morning serum testosterone concentrations within the normal reference range in 92% of patients.
Figure 3 shows the mean (SD) steady-state serum testosterone concentrations during nightly application of Androderm® 2.5 mg/day systems in 29 hypogonadal male patients, 27 patients used 2 systems nightly, and 2 patients used 3 systems nightly. The area between the dashed lines shows the 95% confidence interval for the circadian variation observed in healthy men.
Figure 3. Mean (SD) Steady-State Serum Total Testosterone Concentration (ng/dL)
