Pharmacology Update

Testosterone Buccal System (Striant)

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD

The FDA has approved the first transbuccal delivery system for testosterone replacement therapy in men. Like injection and transdermal testosterone preparations, transbuccal testosterone bypasses hepatic first-pass metabolism that limits the use of oral preparations. The patented delivery system is called Bioadhesion Delivery System. Transbuccal testosterone is marketed by Columbia Laboratories as Striant.

Indications

The testosterone buccal system is indicated for replacement therapy in males with deficiency or absence of endogenous testosterone. These include primary hypogonadism (congenital or acquired), testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchidectomy, Klinefelter’s syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. It is also indicated for secondary hypogonadism including hypogonadotropic hypogonadism (congenital or acquired), idiopathic gonadotropin or LHRH deficiency, or pituitary hypothalamic injury from tumors, trauma, or radiation.1

Dosage

The recommended dose is 1 buccal system (30 mg) placed in the gum region twice daily, morning and evening about 12 hours apart.1 The system should be placed just above the incisor tooth and application should be alternated between each side of the mouth. It should be held firmly in place with a finger over the lip and against the product for 30 seconds. If the buccal system is dislodged from the gum surface during the 12-hour period a new system should be applied. If the system is dislodged within 4 hours of the next dose the new system should be applied and remain in place until the next scheduled dosing.1 Testosterone buccal system is available as 30-mg units.

Potential Advantages

This transbuccal delivery system provides an alternative to the patches, gel, or injectable testosterone formulations.

Potential Disadvantages

The most common side effects reported in the phase III 12-week trial were gum or mouth irritation (9.2%), gum tenderness or pain (3.1%), bitter taste (4.1%), gum edema (2%), headache (3.1%), and taste perversion (2%).1 Four of 98 patients (4.1%) discontinued treatment due to gum- or mouth-related adverse events.1

Comments

Striant is the newest delivery system for testosterone. The tablet is placed in the natural depression where the gum meets the upper lip above the incisor teeth. The small, gel-like monoconvex tablet adheres to mucosal surface and remains over a 12-hour period. Testosterone is released and absorbed into the systemic circulation bypassing the liver (ie, first-pass metabolism).2 Mean total testosterone levels produced by Striant are within normal physiologic range (mean average concentration ranged from 520 to 550 ng/dL) and are similar to those produced by other testosterone formulations such as the patch, gel, and injection.1,3 FDA approval was supported by a phase III, open-label, parallel, 12-week study with 98 study subjects. Most common side effects were gum irritation, pain, edema or tenderness, mouth irritation, bitter taste or taste perversion, and headache. Gum irritation generally resolved in 1-8 days and gum tenderness in 1-14 days.1 The wholesale cost for Striant is about $5 per day and similar to that for the transdermal system (eg, Androderm) and the gel (eg, AndroGel).

Clinical Implications

Striant offers another option to the delivery of testosterone. Current formulations include Intramuscular injection, transdermal delivery systems (scrotal and nonscrotal), and topical gel. Bioavailability is poor orally due to poor solubility and extensive first-pass metabolism. Low testosterone levels have been associated with muscle atrophy and weakness, osteoporosis, increase in fat mass, depression, and sexual dysfunction. Some uses of testosterone replacement, however, are controversial and are often fueled by patient demand. In a recent survey about 90% of members of the American Association of Clinical Endocrinologists were concerned about potential abuse of testosterone.4 The decision to treat often comes down to a benefit vs risk analysis, not so much in truly hypogonadal young men but more so with older men with normal or low-normal testosterone levels. A recent review suggests that testosterone replacement is warranted in older men with a significant decline in testosterone level regardless of symptoms and those with mildly decreased testosterone levels with symptoms of hypogonadism (eg, osteoporosis, sexual dysfunction). Potential risks include increased incidence of sleep apnea, stimulation of previously unseen prostate cancer, and elevation of prostate-specific antigen (PSA).4 There has been no study longer than 3 years.3 The Institute of Medicine has been called upon to help design a large-scale trial to help clarify these important issues.

Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente, and Assistant Clinical Professor of Medicine, University of California-San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Both are associate editors of Internal Medicine Alert.

References

1. Striant Product Information. Columbia Laboratories. June 2003.

2. www.columbialab.com

3. Grunenewald DA, Matsumoto AM. J Am Geriatr Soc. 2003;51:101-115.

4. Vastag B. JAMA. 2003;289:971-972.