Becaplermin

AND PRECAUTIONS The most common side effect of becaplermin is a rash that can develop on the skin where it is applied. Other important side effects caused by the drug include redness of the skin called erythema, a skin ulcer with possible infection and pain at the location where the drug is applied. An increased risk of developing cancer or dying from cancer has been reported with becaplermin use. The drug should be used with caution in individuals with a history of cancer.

Gel: 0.01%

Becaplermin should be stored in a refrigerator at 2 C to 8 C (36 F to 46 F). It should not be frozen and should not be used after the expiration date imprinted on the tube.

Mechanism Of Action

REGRANEX Gel has biological activity similar to that of endogenous platelet-derived growth factor, which includes promoting the chemotactic recruitment and proliferation of cells involved in wound repair and enhancing the formation of granulation tissue.

Pharmacodynamics

Clinical pharmacodynamic studies have not been conducted.

Pharmacokinetics

Ten patients with Stage III or IV (as defined in the International Association of Enterostomal Therapy (IAET) guide to chronic wound staging,1,2 lower extremity diabetic ulcers received topical applications of becaplermin gel 0.01% at a dose range of 0.32–2.95 μg/kg (7μg/cm²) daily for 14 days. Six patients had non-quantifiable PDGF levels at baseline and throughout the study, two patients had PDGF levels at baseline which did not increase substantially, and two patients had PDGF levels that increased sporadically above their baseline values during the 14 day study period.

Clinical Studies

The effects of REGRANEX Gel on the incidence of and time to complete healing in lower extremity diabetic ulcers were assessed in four randomized controlled studies. Of 922 patients studied, 478 received either REGRANEX Gel 0.003% or 0.01%. All study participants had lower extremity diabetic neuropathic ulcers that extended into the subcutaneous tissue or beyond (Stages III and IV of the IAET guide to chronic wound staging). Ninety-three percent of the patients enrolled in these four trials had foot ulcers. The remaining 7% of the patients had ankle or leg ulcers. The diabetic ulcers were of at least 8 weeks duration and had an adequate blood supply (defined as TcpO2 > 30 mm Hg). In the four trials, ninety-five percent of the ulcers measured in area up to 10 cm², and the median ulcer size at baseline ranged from 1.4 cm² to 3.5 cm². All treatment groups received a program of good ulcer care consisting of initial complete sharp debridement, a non-weight-bearing regimen, systemic treatment for woundrelated infection if present, moist saline dressings changed twice a day, and additional debridement as necessary. REGRANEX Gel 0.003% or 0.01% or placebo gel was applied once a day and covered with a saline moistened dressing. After approximately 12 hours, the gel was gently rinsed off and a saline moistened dressing was then applied for the remainder of the day. Patients were treated until complete healing, or for a period of up to 20 weeks. Patients were considered a treatment failure if their ulcer did not show an approximately 30% reduction in initial ulcer area after eight to ten weeks of REGRANEX Gel therapy.

The primary endpoint, incidence of complete ulcer closure within 20 weeks, for all treatment arms is shown in Figure 1. In each study, REGRANEX Gel in conjunction with good ulcer care was compared to placebo gel plus good ulcer care or good ulcer care alone.

In Study 1, a multicenter, double-blind, placebo controlled trial of 118 patients, the incidence of complete ulcer closure for REGRANEX Gel 0.003% (n=61) was 48% versus 25% for placebo gel (n=57; p=0.02, logistic regression analysis).

In Study 2, a multicenter, double-blind, placebo controlled trial of 382 patients, the incidence of complete ulcer closure for REGRANEX Gel 0.01% (n=123) was 50% versus 36% for REGRANEX Gel 0.003% (n=132) and 35% for placebo gel (n=127). Only REGRANEX Gel 0.01% was significantly different from placebo gel (p=0.01, logistic regression analysis).

The primary goal of Study 3, a multicenter controlled trial of 172 patients, was to assess the safety of vehicle gel (placebo; n=70) compared to good ulcer care alone (n=68). The study included a small (n=34) REGRANEX Gel 0.01% arm. Incidences of complete ulcer closure were 44% for REGRANEX Gel, 36% for placebo gel and 22% for good ulcer care alone.

In Study 4, a multicenter, evaluator-blind, controlled trial of 250 patients, the incidences of complete ulcer closure in the REGRANEX Gel 0.01% arm (n=128) (36%) and good ulcer care alone (n=122) (32%) were not statistically different.

Figure 1: Incidence of Complete Healing

In general, where REGRANEX Gel was associated with higher incidences of complete ulcer closure, differences in the incidence first became apparent after approximately 10 weeks and increased with continued treatment (Table 3).

Table 3: Life Table Estimates of the Incidence (%) of Complete Healing over Time of Study 2

In a 3-month follow-up period where no standardized regimen of preventative care was utilized, the incidence of ulcer recurrence was approximately 30% in all treatment groups, demonstrating that the durability of ulcer closure was comparable in all treatment groups.

In a randomized, double-blind study of REGRANEX Gel (100 mcg/g once daily for 16 weeks) in patients with Stage III or IV pressure ulcers, the incidence of complete ulcer closure was 15% (28/189) in the becaplermin group and 12% (22/190) in the vehicle control group. This difference was not statistically significant.

In two small, randomized, double-blinded studies of REGRANEX Gel (100 mcg/g once daily for 16 weeks) in patients with venous stasis ulcers, the combined incidence of complete ulcer closure was 46% (30/65) in the becaplermin group and 39% (26/67) in the vehicle control group. This difference was not statistically significant.

REFERENCES

1. J. Enterostomal Ther 15:4, 1988

2. Decubitus 2:24, 1989

Becaplermin is part of the drug class:

• Other cicatrizants

Use this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The amount of becaplermin gel to be applied will vary depending upon the size of your ulcer. Your doctor will measure your ulcer to calculate the amount of gel you need to use. 

Your doctor or wound care giver will check your ulcer every 1 or 2 weeks to determine if the amount of gel used needs to be changed.

Keep this and all medicines out of the reach of children.

Store becaplermin gel in the refrigerator (36°F to 46°F). Do not freeze it.

Becaplermin gel should not be used after the expiration date on the bottom end of the tube.

Throw away any becaplermin gel that is out of date or no longer needed for your treatment.

• Store in a refrigerator. Do not freeze.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

Diabetic ulcers (lower extremity): Adolescents ≥16 years: Refer to adult dosing

There are no dosage adjustments provided in the manufacturer's labeling. However, dosage adjustment unlikely due to low systemic absorption.

You should not use this medication if you are allergic to becaplermin or parabens, or if you have skin cancer affecting your feet. Do not apply becaplermin over any wound or surgical incision that has been closed with stitches, staples, or surgical tape.

FDA pregnancy category C. It is not known whether becaplermin will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

It is not known whether becaplermin topical passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Do not use this medication on a child younger than 16 years old.

Some people who used 3 or more courses of treatment with becaplermin topical have developed cancer. However, it is not known whether this medication actually causes cancer. Talk with your doctor about your own specific cancer risk.