Becaplermin

REGRANEX is indicated for the treatment of lower extremity diabetic neuropathic ulcers that extend into the subcutaneous tissue or beyond and have an adequate blood supply, when used as an adjunct to, and not a substitute for, good ulcer care practices including initial sharp debridement, pressure relief and infection control. Limitations of Use: The efficacy of REGRANEX has not been established for the treatment of pressure ulcers and venous stasis ulcers [ see Clinical Studies ( 14.2 ) ] and has not been evaluated for the treatment of diabetic neuropathic ulcers that do not extend through the dermis into subcutaneous tissue [Stage I or II, International Association of Enterostomal Therapy (IAET) staging classification] or ischemic diabetic ulcers. The effects of becaplermin on exposed joints, tendons, ligaments, and bone have not been established in humans [ see Nonclinical Toxicology ( 13.2 ) ]. REGRANEX is not intended to be used in wounds that close by primary intention. REGRANEX is a human platelet-derived growth factor indicated for the treatment of lower extremity diabetic neuropathic ulcers that extend into the subcutaneous tissue or beyond and have an adequate blood supply. REGRANEX is indicated as an adjunct to, and not a substitute for, good ulcer care practices. ( 1 ) Limitations of Use: The efficacy of REGRANEX has not been established for the treatment of pressure ulcers and venous stasis ulcers. ( 1 ) The effects of REGRANEX on exposed joints, tendons, ligaments, and bone have not been established in humans. ( 1 ) REGRANEX is not intended to be used in wounds that close by primary intention. ( 1 )

Gel: 0.01%; clear, colorless to straw-colored Gel: 0.01% ( 3 )

REGRANEX is contraindicated in patients with known neoplasm(s) at the site(s) of application. Known neoplasm(s) at the site(s) of application ( 4 )

Malignancies distant from the site of application have been reported in both a clinical study and in postmarketing use. ( 5.1 ) The benefits and risks of REGRANEX treatment should be carefully evaluated before prescribing in patients with known malignancy. ( 5.1 )

5.1 Risk of Cancer REGRANEX contains becaplermin, a recombinant human platelet-derived growth factor, which promotes cellular proliferation and angiogenesis [ see Clinical Pharmacology ( 12.1 ) ]. Malignancies distant from the site of application have occurred in REGRANEX users in a clinical study and in postmarketing use [ see Adverse Reactions ( 6.1 ) and Clinical Studies ( 14.3 ) ]. The benefits and risks of REGRANEX treatment should be carefully evaluated before prescribing in patients with known malignancy.

5.2 Application Site Reactions If application site reactions occur, the possibility of sensitization or irritation caused by parabens or m-cresol should be considered. Consider interruption or discontinuation and further evaluation (e.g. patch testing) as dictated by clinical circumstances.

Erythematous rashes occurred in 2% of patients treated with REGRANEX. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch, or Lynch Regenerative Medicine, LLC at 1-888-576-7343

6.1 Clinical Trials 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. In clinical trials, erythematous rashes occurred in 2% of subjects treated with REGRANEX (and good ulcer care) or placebo (and good ulcer care), and none in subjects receiving good ulcer care alone. Subjects treated with REGRANEX did not develop neutralizing antibodies against becaplermin. In a retrospective follow-up study of 491 of 651 subjects (75%) from two randomized, controlled trials of another formulation of becaplermin gel 0.01%, the subjects were followed for a median of approximately 20 months to evaluate safety and recurrence of healed diabetic lower extremity ulcers. Eight of 291 subjects (2.7%) from the becaplermin gel group and two of 200 subjects (1%) from the vehicle/standard of care group were diagnosed with cancers during the follow-up period, a relative risk of 2.7 (95% confidence interval [CI], 0.6-12.8). The types of cancers varied and all were remote from the treatment site [see Warnings and Precautions ( 5.1 )] .

6.2 Postmarketing Experience Because post-approval adverse 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 the drug. The following adverse reactions have been identified during post approval use of REGRANEX. Increased rate of death from systemic malignancies in patients dispensed 3 or more tubes of REGRANEX was observed in one of three retrospective postmarketing studies [ see Clinical Studies ( 14.3 ) ]. Burning sensation and erythema at the site of application have been reported.

It is not known if REGRANEX interacts with other topical medications applied to the ulcer site. The use of REGRANEX with other topical drugs has not been studied.

8.1 Pregnancy Risk Summary There are no available data on REGRANEX use in pregnant women to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted with REGRANEX. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

8.2 Lactation There are no data on the presence of becaplermin in human milk, the effects on the breastfed infant, or the effects on milk production after topical application of REGRANEX to lactating women. The developmental and health benefits of breastfeeding should be considered along with the lactating woman's clinical need for REGRANEX and any potential adverse effects on the breastfed child from becaplermin.

8.4 Pediatric Use Safety and effectiveness of REGRANEX in pediatric patients below the age of 16 years have not been established.

8.5 Geriatric Use Among subjects receiving any dose of REGRANEX in clinical studies of diabetic lower extremity ulcers, 150 subjects were 65 years of age and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. The number of subjects aged 75 and older was insufficient (n=34) to determine whether they respond differently from younger subjects.