Data Sheet
REGRANEXTM
Becaplermin 0.01% gel
Presentation
REGRANEX contains 100 micrograms of becaplermin per gram of gel. Becaplermin is the recombinant BB homodimer of human Platelet Derived Growth Factor (PDGF). PDGF is a dimeric protein with a molecular weight of approximately 24,500 daltons.
REGRANEX is available in multi-use tubes as a colourless to straw-coloured gel with a preservative that allows for daily topical use. It also contains carmellose sodium, sodium chloride, sodium acetate, glacial acetic acid, methyl hydroxybenzoate, propyl hydroxybenzoate, meta-Cresol, lysine hydrochloride and water.
Uses
Action:
REGRANEX contains becaplermin, a recombinant human PDGF. It has biological activity similar to that of naturally occurring PDGF, which includes promoting the chemotactic recruitment and proliferation of cells involved in wound repair. In animal wound models, the predominant effect of becaplermin is to enhance the formation of granulation tissue.
Pharmacokinetics
Systemic absorption of becaplermin from topically applied REGRANEX was studied. Following 14 consecutive daily topical applications to ulcers, no consistent increase in plasma PDGF-BB concentration above pre-treatment concentrations and no concentrations above endogenous PDGF-BB levels were observed.
Indications
REGRANEX is indicated in association with other good wound care measures, to promote granulation and thereby the healing of full thickness neuropathic chronic diabetic ulcer less than or equal to 10cm².
Dosage and Administration
REGRANEX should always be used in conjunction with good wound care consisting of initial debridement (to remove all the necrotic and /or infected tissue), additional debridement as necessary and a non weight-bearing regimen to alleviate pressure on the ulcer. Wound related infection should be identified and treated with appropriate antimicrobial therapy prior to use of REGRANEX. Prior to the use of REGRANEX, related underlying conditions such as osteomyelitis and peripheral arteriopathy should be excluded or treated if present. Osteomyelitis should be assessed by X-ray examination. Peripheral arteriopathy should be excluded by assessment of the pedal pulses or other techniques. Ulcers with a suspicious appearance should be biopsied to exclude malignancy.
REGRANEX should be applied as a continuous thin layer to the entire ulcerated area(s) once daily using a clean application aid. The site(s) of application should then be covered by a moist saline gauze dressing that maintains a moist wound-healing environment. REGRANEX should not be used in conjunction with occlusive dressings.
REGRANEX should be used for a period not exceeding 20 weeks in total in any individual patient.
If during the treatment with REGRANEX no meaningful healing progress is evident after the first ten weeks of continuous therapy, treatment should be re-evaluated, and factors known to compromise healing (such as osteomyelitis, ischaemia, infection) should be reassessed. Therapy should be continued to the maximum of 20 weeks as long as healing progress is seen on periodic evaluation.
REGRANEX is not intended for repeated use.
Contraindications
REGRANEX is contraindicated in patients with:
- known hypersensitivity to any component of this product,
- neoplasm(s) at the site(s) of application.
Warning and Precautions
Use with caution in the following circumstances:
Potential for systemic growth factor effects
Although the potential for systemic absorption of becaplermin from sites of topical application is low, REGRANEX should be used with caution in patients with malignancies.
Malignancies distant from the site of application have occurred in becaplermin users in both a clinical study and in postmarketing use. A population-based postmarketing study did not find an increase in cancer incidence or cancer mortality among patients exposed to REGRANEX Gel, but did find an increased rate of death from systemic malignancies in patients who received 3 or more tubes of REGRANEX Gel. Further mortality follow-up, not part of the original study plan, did not support the earlier mortality finding.
Use in pregnancy (Category B.2)
Since absorption is negligible from the site of topical application, animal reproductive toxicity studies have not been conducted with REGRANEX. No studies in pregnant women have been conducted. Therefore, REGRANEX should be used with caution in pregnant women.
Use in lactation
It is not known whether becaplermin is excreted in human milk. Therefore, REGRANEX should be used with caution in nursing mothers.
Paediatric use
Safety and effectiveness in children and adolescents below the age of 18 years have not been established.
Carcinogenicity / Mutagenicity
Beceplermin was not mutagenic or clastrogenic in a battery of in vitro and in vivo tests. Carcinogenicity studies were not conducted due to the lack of mutagenic or clastrogenic potential. Also, reproductive toxicity studies were not conducted due to negligible systemic absorption following topical application. In a bone-toxicity study in rats, beceplermin produced histomorphologic changes (periosteal hyperplasia, subperiosteal bone resorption, formation and exostosis) suggestive of accelerated bone remodelling, which was deemed to be a transient phenomenon and not unexpected given the compound's pharmacological ability to stimulate connective tissue (fibroplasia with accompanying mononuclear cell infiltration) growth.
Effects on ability to drive and use machines
There are no undesirable effects known at this time.
Adverse Reactions
Studies analysed to date indicate that REGRANEX is generally well tolerated.
One thousand and six subjects with diabetic neuropathic ulcers were treated with either becaplermin gel (538 subjects), vehicle gel (278 subjects) or standard wound care (190 subjects) in six well-controlled, blinded trials. Overall, the incidence of subjects experiencing at least one treatment-emergent adverse event was comparable for subjects treated with all doses of becaplermin gel (66%), becaplermin gel 100μg/g (70%), vehicle gel (67%) or standard wound care (81%). The majority of treatment-emergent adverse events reported in these studies were related to the subjects' diabetic ulcers or their underlying diabetes and most often affected the skin and appendages, resistance mechanisms, and the body as a whole. These included disorders such as skin ulceration, infection, cellulitis, pain and osteomyelitis. In general, the incidences of these common treatment-emergent adverse events were similar in patients treated with becaplermin (rys), placebo gel and good wound care alone Rash was reported with patients treated with REGRANEX Gel and placebo gel, with similar incidence but was not reported among patients receiving good wound care alone.
The serious adverse events reported in these clinical trials with becaplermin gel represented common symptoms in this patient population. Among subjects in the completed, double-blinded, well-controlled studies, the incidence of serious adverse events was slightly higher in the standard wound care group (28%) than in the vehicle (25%) or becaplermin gel (all doses) groups (24%). The most frequently reported serious adverse events were cellulitis, osteomyelitis, infection and peripheral ischaemia.
Interactions with other drugs
It is not known whether REGRANEX interacts with other topical medications applied to the ulcer site. Consequently, it is recommended that REGRANEX not be applied to the ulcer site in conjunction with other topical medications.
Overdosage
Since absorption is negligible from the site of topical application, no systemic events are expected.
Pharmaceutical Precautions
Storage
Store refrigerated, 2-8°C (36-46°F), DO NOT FREEZE. REGRANEX should be used within 2 months after opening the seal of the tube.
Medicine Classification
Prescription Only Medicine
Package Quantity
15g multi use tube
New Zealand Sponsor
Johnson & Johnson (New Zealand) Ltd,
Ground Floor, Ericsson House
105 Carlton Gore Road, Newmarket
Auckland, NEW ZEALAND
Date of Preparation:
5 March 2009