International journal of pharmaceutical compounding

G E N E R A L I N T E R E S T
Transdermal Nifedipine
for Wound Healing: Case Reports
Introduction
Michael J. Torsiello, MD
Midland Park, New Jersey
We are treating a number of patients with difficult-to-heal wounds that are refractory to standard forms of treatment, and we Matthew H. Kopacki, RPh, FIACP, FACA, FACVP
are seeing positive results with the addition of transdermal nifedip- Rock Ridge Pharmacy, Glen Rock, New Jersey ine to our traditional course of therapy. This is illustrated in thefollowing case reports.
veloped over the medial aspect of the foot that pulled the foot outof alignment. In addition, a number of other medial and lateral scars on the patient’s foot included a large hypertrophic scar on the lat- A 43-year-old woman with a history of juvenile diabetes melli- eral side, which compromised blood supply to the area. To correct tus for many years presented 7 years ago with significant diabetes this problem and release the contracture, it was necessary to insert breakdown that included macular degeneration, neuroretinal andvascular problems, diabetic neuropathy, and a nonhealing wound on the right heel. The patient was unable to perceive sensation inher foot and had actually walked through the skin of her heel sothat bone was exposed. The vascular supply to the area was extremelypoor as a result of the chronic diabetes, and osteomyelitis wasnoted in the calcaneus. Maggots were applied to debride the necrot-ic tissue to ensure the salvage of the maximum quantity of viabletissue, after which a limb-salvage procedure consisting of insertionof an external fixator and application of a cross-leg flap was initi-ated. Three weeks later during a follow-up procedure, it was notedthat the wound had healed, but several other breakdowns on bothlegs necessitated continuing treatment that included a whittling awayof osteomyelitic bone and debridement of nonviable soft tissue. Inthe interim, the patient had become dialysis dependent. Becauseof the extended healing time required by the recurring wounds, long-term repeated hospitalizations, and wound care, we decided to usetransdermal nifedipine to accelerate healing by inducing localized Note the gray, dusky skin (the area treated) above the lower vasodilation without systemic effects. A dosage of 80 mg nifedip- vertical incision and to the left of the upper incision. ine (1 mL of 8% nifedipine in Pluronic® lecithin organogel [PLO])was prescribed to be administered by the patient twice a day. The gel was dispensed in a 30-mL syringe.
The patient began using the gel on February 10, 1999, and we ob- served a decrease in healing time (depending on wound size) fromas long as 4 to 5 months to within 6 to 8 weeks. No adverse effectswere observed with this therapy. Our concern was the potential forrapid systemic absorption and blood-pressure complications; how-ever, none was noted in the course of therapy. Because the patientis still ambulatory, she continues to experience repeated tissue break-down on both feet. She is now on a waiting list to undergo both akidney and pancreas transplant, and we continue to treat repeatedbreakdowns with nifedipine and routine therapy to facilitate havingclosed wounds in time for the kidney and pancreatic transplantation.
An 8-year-old boy with a clubfoot was referred by an orthope- Approximately 10 to 14 days after the initiation of therapy with dic surgeon. The patient had undergone a foot-straightening pro- nifedipine. The gray skin color (Figure 1) is more pink, which cedure 2 years earlier; however, good union of the bones had not indicates renewed vascularization of the compromised area. The been achieved, and a linear hypertrophic scar contracture had de- International Journal of Pharmaceutical Compounding 356 Vol.4 No.5 September/October 2000
G E N E R A L I N T E R E S T
a tissue expander in the scar, which was on the dorsum of the foot.
prescribed for application (~ 1 mL twice a day) by the patient’s moth- This was accomplished, and the expander was left in place for 4 days.
er. Daily whirlpool therapy was also prescribed in addition to gel Bowing of the foot and the tightness of the scar over the integral application twice a day. After 3 weeks of following this regimen, port of the expander caused a pressure necrosis of the skin over the complete healing was observed (Figures 3 and 4). dorsum within 4 postoperative days (Figure 1). When the expander Approximately 10 weeks was allowed for healing, after which the was removed, the area was treated with transdermal nifedipine to patient underwent the second insertion of an expander. Four weeks accelerate wound healing and prevent the formation of another hy- after that procedure, weekly expansion was initiated for 4 to 6 pertrophic scar so that a second tissue expander could be inserted weeks. The large scar on the side of the foot was excised by an or- in the same area (Figure 2). We also did not want to protract the thopedic surgeon. In March of 1999, the bones were refractured, orthopedic procedure. A nifedipine 2% (20 mg/mL) PLO gel was repinned, and straightened; a multiple W-plasty was performed thatcreated a zigzagged scar intended to heal in a nonlinear manner todistribute forces along a greater surface area; a rotation flap was applied; and the foot was immobilized in a cast. The cast was cut1 week after surgery so that the wound could be examined. Areaswith vascular compromise were observed; this was not unexpect-ed because of the nature of the multiple procedures that had beenperformed. Transdermal nifedipine was again prescribed as previ-ously described, and complete wound healing occurred in 3 to 4weeks. The patient is now ambulatory with a straightened foot.
Discussion
Nifedipine, a calcium channel blocker used as an antianginal, pre- vents the development of both motor deficits and sensory nerve-con-duction-velocity deficits in streptozotocin-diabetic rats.1 The exactmechanism of action remains to be determined. The beneficial ef-fects of nifedipine without concomitant changes in nerve hypoxic re-sistance or capillarization have been observed. It has been suggest-ed that the drug-induced blocking of calcium influx into vascular After several weeks of continuous therapy with nifedipine. smooth muscle may lead to reduced vascular tone,2,3 which could in-crease nerve blood flow.4 We believe that the same smooth muscle relaxation occurs in the skin vasculature and creates a localized pe-ripheral vasodilation and increased flow to the localized area, whichaccelerates epithelialization and possible microvascular neogenesis.
Theoretically, nifedipine could lower blood pressure and cause bradycardia and related symptoms, but we have seen no evidenceof adverse effects in these 2 patients. The patient described inCase 2 was monitored vigilantly for such changes by his pediatri-cian during treatments. In addition, other patients (even a non-compliant diabetic with uncontrolled blood pressure) have exhib-ited no evidence of lowered blood pressure with this treatment. Thetransdermal application that has been used appears to result in lit-tle-to-no systemic absorption when applied as prescribed. Oneeffect has been noted: dryness of the skin in the area surroundingthe wound. However, we consider this to be a good sign becauseit suggests vasodilatation and epidermolysis in the healed areas. Wehave considered such skin dryness as a criterion in the assessment The patient was recuperating at home when this photo was taken. Proper healing had occurred, and the skin color Because the nifedipine in a traditional PLO gel is somewhat International Journal of Pharmaceutical Compounding 357
G E N E R A L I N T E R E S T
tacky, a vanishing penetrating transdermal cream that provides References
a more elegant and patient-acceptable preparation is now being Robertson S, Cameron NE, Cotter MA. The effect of the calcium antago- substituted as the base. That cream is slightly more emollient than nist nifedipine on peripheral nerve function in streptozotocin-diabetic rats.
nifedipine in PLO gel and may cause fewer signs of dryness.
Diabetologia. 1992;35:1113-1117.
Because the preparation is light sensitive, it is dispensed in an amber Triggle DJ. Biochemical pharmacology of calcium blockers. In: Flaim SF, plastic bag in which the product is to be stored. The patient is in- Zelis R, eds. Calcium Blockers: Mechanism of Actions and Clinical Appli- structed to apply the preparation with a finger cot or a plastic- cations. Baltimore, MD: Williams & Wilkins; 1982:121-134.
wrapped finger to minimize possible systemic absorption.
Flaim SF. Comparative pharmacology of calcium blockers based on stud- This therapy has proven so efficacious that transdermal nifedip- ies of vascular smooth muscle. In: Flaim SF, Zelis R, eds. Calcium Block- ine is now considered another part of our therapeutic armamentarium ers: Mechanism of Actions and Clinical Applications. Baltimore, for limb salvage in a variety of patients.
MD:Williams & Wilkins; 1982:155-178.
Michael J. Torsiello, MD, is a specialist in microsurgery and in Flaim ST, Kanda K. Comparative pharmacology of calcium channel block- plastic, reconstructive, hand, and cosmetic surgery. In addition to ers based on studies of cardiac output distribution. In: Flaim SF, Zelis R, his affiliation with several area hospitals, Dr. Torsiello maintains eds. Calcium Blockers: Mechanism of Actions and Clinical Applications. a private practice in Midland Park and Hoboken, New Jersey. Baltimore, MD: Williams & Wilkins; 1982:179-192. ■ Matthew H. Kopacki, RPh, is the owner of Rock Ridge Pharma- cy in Glen Rock, New Jersey, and serves as externship preceptor atSt. John’s University in Jamaica, New York, and at Rutgers Uni- Address correspondence to: Matthew H. Kopacki, RPh, FIACP, versity in New Brunswick, New Jersey. Rock Ridge Pharmacy, 191 Rock Rd., Glen Rock, NJ, 07452. 17200 East Ohio Drive Aurora, CO 80017 Fax 303-755-5242 International Journal of Pharmaceutical Compounding 358 Vol.4 No.5 September/October 2000

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