Prescribing Information
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Patient description

60-year-old female with uncontrolled type 2 diabetes (HbA1c 12.0%), peripheral neuropathy, and peripheral artery disease (PAD). Using silver sulfadiazine cream and gauze bandage for left foot ulcer that developed from or after an insect bite. Fully ambulatory in post-op shoes. Intermittent sharp pain in left foot.

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Day 1: Negative pressure wound therapy was started.

Ulcer measured: 3.5cm x 3.5cm x 1.5cm

Day 54: Skin graft failure was noted. Ultrasound demonstrated occlusion of bypass graft. Ulcer was sharp debrided and enzymatically debrided, ADAPTIC™, and gauze.

Ulcer measured: 3.2cm x 2.7cm†

† No depth measured; all necrotic tissue removed.

Day 67: Treatment started with hyperbarics; enzymatic debrider.

Ulcer measured: 2.4cm x 2.1cm‡

‡Transcutaneous oxygen measurement (TCOM): 31mm Hg by wound, increased to 44mm Hg on 100% oxygen at sea level.

Day 103

Ulcer measured: 1.8cm x 1.2cm

Day 117: Hyperbaric treatment was completed and treatment with REGRANEX Gel continued for another eight and a half weeks.

Ulcer measured: 1.8cm x 1.2cm

Day 131

Ulcer measured: 1.2cm x 0.5cm

Day 145

Ulcer measured: 0.8cm x 0.2cm

Day 159

Ulcer measured: 0.4cm x 0.2cm

Day 176: Ulcer completely healed.*

Wound presentation

Patient presented with full-thickness ulcer, measuring 3.2cm x 3.2cm x 1.7cm, on left lateral foot over the fifth metatarsal base.

Vascular exam revealed left femoral bruit. Left dorsalis pedis (DP) and popliteal pulses nonpalpable and monophasic with Doppler. Angiogram demonstrated widely patent left common, internal, and external iliac arteries; very mild PAD in left common and superficial femoral artery; 40% focal stenosis of left popliteal artery; occlusion of left anterior tibial artery; left DP filled via collaterals; extensive calcific plaque in peroneal artery with diffuse narrowing; extensive calcific plaque in post-tibial artery.

Treatment

Patient underwent left popliteal to DP artery bypass using in situ greater saphenous vein conduit. Left lateral foot wound was surgically debrided. On Day 1, negative pressure wound therapy was started. A full-thickness skin graft was applied to ulcer. On Day 54, skin graft failure was noted. Ultrasound demonstrated occlusion of bypass graft. Ulcer was sharp debrided and enzymatically debrided with collagenase ointment, ADAPTIC™, and gauze. On Day 67, treatment started with hyperbarics (adequate blood supply to the wound was confirmed); enzymatic debridement was continued. The wound was sharp debrided and hyperbarics continued, and treatment was started with REGRANEX Gel; enzymatic debridement was discontinued. On Day 117, hyperbaric treatment was completed and treatment with REGRANEX Gel continued for another eight and a half weeks. Ulcer was completely healed* on Day 176.

Results* After failure of a skin graft, treatment with good ulcer care and REGRANEX Gel was initiated. Ulcer healed approximately 12 weeks after the initiation of this treatment regimen.

*Individual results will vary.

Case studies contributed by Susie Seaman, NP, MSN, CWOCN.

Patient description

50-year-old male with type 2 diabetes, peripheral neuropathy, peripheral artery disease, left fifth toe amputation for osteomyelitis, stenting of right and left external iliac arteries. Has had recurrent left foot ulcers for three to four years. Fully ambulatory in post-op shoe with cutout under ulcer.

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Day 1: Ulcer was sharp debrided and treatment was started with
REGRANEX Gel. Patient was off-loaded with a post-op shoe and crutches.

Ulcer measured: 1.2cm x 1.0cm x 0.4cm

Day 7: Ulcer was sharp debrided and treatment with REGRANEX Gel continued.

Ulcer measured: 0.9cm x 0.8cm x 0.3cm

Day 17: Ulcer was sharp debrided and treatment with REGRANEX Gel continued.

Ulcer measured: 0.7cm x 0.4cm x 0.1cm

Day 27: Treatment with REGRANEX Gel was discontinued and ulcer was covered with ADAPTIC™ dressing and gauze. Ulcer was completely healed on September 10; order was placed for diabetic shoes for patient.

Ulcer measured: 0.2cm x 0.2cm

Wound presentation

Patient presented with a full-thickness diabetic ulcer, measuring 1.2cm x 1.0cm x 0.4cm, on the plantar surface of the left foot under the first metatarsophalangeal (MTP) joint. Ulcer had 100% granulation, no bone probe, and was surrounded by callus. X-ray was negative for osteomyelitis under ulcer.

Exam revealed left femoral pulse 2+, no bruit. Left popliteal pulse was nonpalpable. Left dorsalis pedis (DP) and posterior tibial (PT) pulses 2+. Left DP was triphasic with Doppler; left PT was biphasic.

Treatment

At initial exam Day 1, ulcer was sharp debrided and treatment was started with REGRANEX Gel. Patient was off-loaded with a post-op shoe and crutches. On Day 7 and Day 17, ulcer was sharp debrided and treatment with REGRANEX Gel continued. On Day 17, treatment with REGRANEX Gel was discontinued, and ulcer was covered with ADAPTIC™ dressing and gauze. Ulcer was completely healed* on Day 27; order was placed for diabetic shoes for patient.

Results* Size of ulcer decreased after just one week of treatment. After five and a half weeks of treatment with less than one tube of REGRANEX Gel and good ulcer care, patient’s diabetic foot ulcer was completely healed.

*Individual results will vary.

Case studies contributed by Susie Seaman, NP, MSN, CWOCN.

Patient description

The patient was presented to ER with DFU. Angiogram to determine vascularity. A week later, sharp debridement was performed. Patient was then discharged to home care with REGRANEX Gel, three days post-debridement with forefoot offloading wedge shoe. Home health nurse monitored patient until seen four weeks later.

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Day 1

Ulcer measured: 3.0cm x 2.5cm x 0.2cm

Day 7

Ulcer measured: 3.0cm x 2.3cm x 0.1cm

Day 14

Ulcer measured: 2.0cm x 1.5cm x 0.1cm

Day 34

Ulcer measured: 2.0cm x 1.0cm x 0.1cm

Day 53

Ulcer measured: 0.2cm x 0.1cm

Day 71: Wound resolved in 2.4 months with initial sharp debridement plus REGRANEX Gel plus offloading.*

Ulcer measured: 0.2cm x 0.1cm

*Individual results will vary.

Clinical study results for REGRANEX Gel

In clinical trials, REGRANEX Gel was found to help wounds heal faster and more completely than placebo.4

Review efficacy data
Formulated for healing

Therapy with REGRANEX Gel initiates healing by attracting repair cells to revitalize wounds.7

Review the MOA
Important Safety Information

Warning: Increased rate of mortality secondary to malignancy
An increased rate of mortality secondary to malignancy was observed in patients treated with 3 or more tubes of REGRANEX (becaplermin) Gel, 0.01% in a postmarketing retrospective cohort study. REGRANEX Gel should only be used when the benefits can be expected to outweigh the risks. REGRANEX Gel should be used with caution in patients with known malignancy.

Indication and limitations of use
REGRANEX Gel 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. REGRANEX Gel is indicated as an adjunct to, and not a substitute for, good ulcer care practices including initial sharp debridement, pressure relief and infection control.

Contraindications
REGRANEX Gel is contraindicated in patients with known neoplasm(s) at the site(s) of application. REGRANEX Gel is contraindicated in patients with known hypersensitivity to any component of the product (eg, parabens).

Warnings and precautions
Malignancies distant from the site of application have been reported in both a clinical study and in postmarketing use. REGRANEX Gel should be used with caution in patients with a known malignancy.

If application site reactions occur, the possibility of sensitization or irritation caused by parabens or m-cresol should be considered.

Commonly observed adverse reactions
In clinical trials, erythematous rashes occurred in 2% of patients treated with REGRANEX Gel (and good ulcer care) or placebo (and good ulcer care), and none in patients receiving good ulcer care alone.

See warnings above regarding malignancy.

Burning sensation at the site of application and erythema have been reported during post-approval use of REGRANEX Gel.

Other important information
The amount of REGRANEX Gel to be applied should be recalculated by the physician or wound caregiver at weekly or biweekly intervals depending upon the rate of change in ulcer area.

If the ulcer does not decrease in size by approximately 30% after 10 weeks of treatment or complete healing has not occurred in 20 weeks, continued treatment with REGRANEX Gel should be reassessed.

Pregnancy and Nursing Mothers: Pregnancy Category C. REGRANEX Gel should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether becaplermin is excreted in human milk. Because many drugs are secreted in human milk, caution should be exercised when REGRANEX Gel is administered to nursing women.

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

Counsel patients to review the Medication Guide and to discuss any questions or concerns with their healthcare provider before starting REGRANEX Gel and at regular intervals during treatment, including when their prescription is refilled.

To report suspected adverse reactions, contact Smith & Nephew at 1-800-441-8227 or contact FDA at www.fda.gov/medwatch or at 1-800-FDA-1088.

Please see accompanying full Prescribing Information and Medication Guide.

Show References
  1. Moulik PK, Mtonga R, Gill GV. Amputation and mortality in new-onset diabetic foot ulcers stratified by etiology. Diabetes Care. 2003;26:491-494.
  2. Armstrong DG, Wrobel J, Robbins JM. Guest editorial: are diabetes-related wounds and amputations worse than cancer? Int Wound J. 2007;4:286-287.
  3. American Cancer Society. Cancer Facts & Figures 2014. Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2014/cancer-facts-and-figures-2014.pdf. Accessed May 5, 2017.
  4. Wieman TJ, Smiell JM, Su Y. Efficacy and safety of a topical gel formulation of recombinant human platelet-derived growth factor-BB (becaplermin) in patients with chronic neuropathic diabetic ulcers. A phase III randomized placebo-controlled double-blind study. Diabetes Care. 1998;21:822-827.
  5. REGRANEX Gel Prescribing Information.
  6. Heldin CH, Westermark B. Mechanism of action and in vivo role of platelet-derived growth factor. Physiol Rev. 1999;79:1283-1316.
  7. Diegelmann RF, Evans MC. Wound healing: an overview of acute, fibrotic and delayed healing. Front Biosci. 2004;9:283-289.
  8. Guo S, DiPietro LA. Factors affecting wound healing. J Dent Res. 2010;89:219-229.
  9. Snyder RJ, Hanft JR. Diabetic foot ulcers—effects on quality of life, costs, and mortality and the role of standard wound care and advanced-care therapies in healing: a review. Ostomy Wound Manage. 2009;55:28-38.
  10. Edmonds M, Foster AV, Vowden P. Wound bed preparation for diabetic ulcers. In: Moffatt C, ed. European Wound Management Association (EWMA). Position Document: Wound Bed Preparation in Practice. London, England: MEP Ltd; 2004:6-11.
  11. Steed DL, Attinger C, Colaizzi T, et al. Guidelines for the treatment of diabetic ulcers. Wound Repair Regen. 2006;14:680-692.
  12. Snyder RJ, Kirsner RS, Warriner RA III, Lavery LA, Hanft JR, Sheehan P. Consensus recommendations on advancing the standard of care for treating neuropathic foot ulcers in patients with diabetes. Ostomy Wound Manage. 2010;56(4 Suppl):S1-S24.
  13. Papanas N, Maltezos E. Benefit-risk assessment of becaplermin in the treatment of diabetic foot ulcers. Drug Saf. 2010;33:455-461.
  14. Falanga V. Wound bed preparation: science applied to practice. In: Moffatt C, ed. European Wound Management Association (EWMA). Position Document: Wound Bed Preparation in Practice. London, England: MEP Ltd; 2004:2-5.
  15. Delamater AM. Improving patient adherence. Clin Diabetes. 2006;24:71-77.
  16. Lantis JC II, Boone D, Gendics C, Todd G. Analysis of patient cost for recombinant human platelet-derived growth factor therapy as the first-line treatment of the insured patient with a diabetic foot ulcer. Adv Skin Wound Care. 2009;22:167-171.
  17. Data on file. Smith & Nephew. October 2012.
  18. Frykberg RG, Zgonis T, Armstrong DG, et al; American College of Foot and Ankle Surgeons. Diabetic foot disorders: a clinical practice guideline (2006 revision). J Foot Ankle Surg. 2006;45(5 Suppl):S1-S66.
  19. Huang ES, Basu A, O’Grady M, Capretta JC. Projecting the future diabetes population size and related costs for the US. Diabetes Care. 2009;32:2225-2229.
  20. Boulton AJ. The diabetic foot: grand overview, epidemiology and pathogenesis. Diabetes Metab Res Rev. 2008;24 Suppl 1:S3-S6.
  21. International Working Group on the Diabetic Foot. Time to act. Available at: https://www.worlddiabetesfoundation.org/sites/default/files/Diabetes%20and%20Foot%20care_Time%20to%20act.pdf. Accessed May 9, 2017.
  22. Adeshara KA, Diwan AG, Tupe RS. Diabetes and complications: cellular signalling pathways, current understanding and targeted therapies. Curr Drug Targets. 2016;17:1309-1328.
  23. Kirsner RS. The standard of care for evaluation and treatment of diabetic foot ulcers. The University of Michigan Medical School. The University of Michigan Health System’s Educational Services for Nursing. Barry University School of Podiatric Medicine 2010. Available at: http://www.barry.edu/includes/docs/continuing-medical-education/diabetic.pdf. Accessed May 5, 2017.

Important Safety Information

WARNING: INCREASED RATE OF MORTALITY SECONDARY TO MALIGNANCY

An increased rate of mortality secondary to malignancy was observed in patients treated with 3 or more tubes of REGRANEX (becaplermin) Gel, 0.01% in a postmarketing retrospective cohort study. REGRANEX Gel should only be used when the benefits can be expected to outweigh the risks. REGRANEX Gel should be used with caution in patients with known malignancy.

Important Safety Information

People who use 3 or more tubes of REGRANEX (becaplermin) Gel may have an increased risk of death from cancer.

You should talk with your healthcare provider about the possible benefits and risks to you if you use more than 3 tubes of REGRANEX Gel. If you already have cancer, you and your healthcare provider should carefully consider whether you will use REGRANEX Gel.