ALERT: U.S. Boxed Warning The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Special Alerts Becaplermin (Regranex®) Gel: New Boxed Warning (Associated With Increased Risk of Mortality From Cancer in Diabetic Patients) - June 2008
The Food and Drug Administration (FDA) has issued a follow-up Dear Healthcare professional letter regarding an earlier safety review of becaplermin, a recombinant human platelet-derived growth factor. In March, 2008 the FDA announced that it had received information from a retrospective study and was investigating the possibility of an increased risk of cancer and/or mortality from cancer in patients with diabetes who used becaplermin, compared to patients who did not use becaplermin. The FDA has completed its review of this study, suggesting an increased risk of mortality from cancer in patients who used ≥3 tubes of becaplermin gel. As a result, the becaplermin prescribing information has been updated to include a new boxed warning regarding this finding. It is important to note that while the study showed an increase in mortality from cancer, the number of mortalities were small, there was no overall increase in the incidence of cancer, and the observed malignancies were remote from the ulcer treatment site. The FDA recommends the use of becaplermin only when the potential benefits outweigh the risks.
For more information, see http://www.fda.gov/medwatch/safety/2008/safety08.htm#Regranex
Medication Safety Issues Sound-alike/look-alike issues:
Regranex® may be confused with Granulex®, Repronex®
Pronunciation (be KAP ler min)
U.S. Brand Names Regranex®
Canadian Brand Names Regranex®
Pharmacologic Category Growth Factor, Platelet-derived; Topical Skin Product
Use: Labeled Indications Adjunctive treatment of diabetic neuropathic ulcers occurring on the lower limbs and feet that extend into subcutaneous tissue (or beyond) and have adequate blood supply
Dosing: Adults Diabetic ulcers (lower extremity): Topical: Apply appropriate amount of gel once daily with a cotton swab or similar tool, as a coating over the ulcer. The amount of becaplermin to be applied will vary depending on the size of the ulcer area.
Note: If the ulcer does not decrease in size by ~30% after 10 weeks of treatment or complete healing has not occurred in 20 weeks, continued treatment with becaplermin gel should be reassessed.
Estimation of gel requirement: To calculate the length of gel applied to the ulcer, measure the greatest length of the ulcer by the greatest width of the ulcer. Tube size and unit of measure will determine the formula used in the calculation. Recalculate amount of gel needed every 1-2 weeks, depending on the rate of change in ulcer area.
Centimeters:
15 g tube: [ulcer length (cm) x width (cm)] divided by 4 = length of gel (cm)
2 g tube: [ulcer length (cm) x width (cm)] divided by 2 = length of gel (cm)
Inches:
15 g tube: [length (in) x width (in)] x 0.6 = length of gel (in)
2 g tube: [length (in) x width (in)] x 1.3 = length of gel (in)
Dosing: Elderly Refer to adult dosing.
Administration: Topical For external use only. Squeeze appropriate amount of gel onto clean measuring surface (eg, wax paper), spread onto entire ulcer area in a thin, continuous layer ~1/16 inch thick. Cover with saline moistened dressing; leave dressing in place ~12 hours. After 12 hours, remove dressing, rinse with saline or water to remove residual becaplermin gel and cover with saline moistened dressing (without becaplermin gel) for remainder of the day. Continue use once daily until ulcer is completely healed.
Storage Refrigerate at 2°C to 8°C (36°F to 46°F); do not freeze.
Contraindications Hypersensitivity to becaplermin or any component of the formulation; known neoplasm(s) at the site(s) of application
Warnings/Precautions Boxed warnings:
• Malignancy: See “Concerns related to adverse effects†below.
Concerns related to adverse effects:
• Malignancy: [U.S. Boxed Warning]: An increase in mortality secondary to systemic malignancies has been observed in a retrospective study of patients treated with ≥3 tubes of becaplermin. Malignancies of varying types have been reported; all were remote from the becaplermin treatment site. Use with caution in patients with known malignancy.
Special populations:
• Pediatrics: Safety and efficacy have not been established in children <16 years of age.
Other warnings/precautions:
• Appropriate use: For external use only; do not use in wounds that close by primary intention. Use with caution in ulcer wounds related to arterial or venous insufficiency and when there are thermal, electrical, or radiation burns at wound site. Effects on exposed joints, tendons, ligaments and bone have not been established.
Geriatric Considerations No specific information for use in elderly.
Pregnancy Risk Factor C
Pregnancy Considerations Animal reproduction studies have not been conducted. Use in pregnancy only if clearly needed.
Lactation Excretion in breast milk unknown/use caution
Adverse Reactions 1% to 10%: Dermatologic: Erythematous rash (2%)
<1%: Erythema with purulent discharge, ulcer infection, tunneling of ulcer, exuberant granulation tissue, local pain, skin ulceration
Drug Interactions There are no known significant interactions.
Monitoring Parameters Ulcer volume (pressure ulcers); wound area; evidence of closure; drainage (diabetic ulcers); signs/symptoms of toxicity (erythema, local infections)
Dosage Forms Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Gel, topical:
Regranex®: 0.01% (2 g, 15 g)
Generic Available No
Manufacturer Ortho-McNeil Pharmaceutical, Inc
Pricing: U.S. (www.drugstore.com) Gel (Regranex)
0.01% (15): $642.55
Mechanism of Action Recombinant B-isoform homodimer of human platelet-derived growth factor (rPDGF-BB) which enhances formation of new granulation tissue, induces fibroblast proliferation and differentiation to promote wound healing; also promotes angiogenesis.
Pharmacodynamics/Kinetics Onset of action: Complete healing: 15% of patients within 8 weeks, 25% at 10 weeks
Absorption: Minimal
Distribution: Binds to PDGF beta-receptors in normal skin and granulation tissue
Dental Health: Effects on Dental Treatment No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions No information available to require special precautions
Mental Health: Effects on Mental Status None reported
Mental Health: Effects on Psychiatric Treatment None reported
Index Terms Recombinant Human Platelet-Derived Growth Factor B; rPDGF-BB
References Seeger JD, Fife D, Ziyadeh N, et al, “A Cohort Study of the Risk of Cancer in Regranex (Becaplermin) Users and Matched Comparators,†Pharmacoepidemiol Drug Saf, 2007, 16(S2):167-8:353 [abstract of the 23rd ICPE]
International Brand Names Regranex (AT, BE, BG, CH, CZ, DE, DK, ES, FI, FR, GB, GR, HN, IE, IL, IT, KP, MX, NL, NO, PL, PT, RU, SE, TR)
Copyright (c) Lexi-Comp, Inc. 1978-2008 All Rights Reserved. Sources : Drug Information Handbook, 17th Edition
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