What medications can prevent wound healing?

Medications That Can Prevent Wound Healing

Corticosteroids, immunosuppressive agents (mycophenolate mofetil, azathioprine, cyclosporine, tacrolimus), biologic DMARDs, NSAIDs, and anticoagulants are the principal medications that delay wound healing and should be managed carefully in the perioperative period.

Corticosteroids

Corticosteroids are the most well-established medications that impair wound healing through multiple mechanisms:

• Corticosteroids significantly impair wound healing by decreasing activation and infiltration of inflammatory cells (macrophages and polymorphonuclear leukocytes) that are essential in the first phase of healing 1
• They inhibit expression of growth factors and matrix proteins, including collagen synthesis 1
• Corticosteroids lower transforming growth factor-beta (TGF-β) and insulin-like growth factor-I (IGF-I) levels in wound fluid and reduce hydroxyproline (collagen) content in healing tissue 2
• Both topical and systemic corticosteroids significantly retard wound healing, with medium-strength topical steroids (fluocinolone) having greater inhibitory effects than weak steroids (hydrocortisone) 3
• Long-term use of corticosteroids >15 mg/day prednisone increases risk of wound infection and dehiscence 1
• Even low-dose corticosteroids (<5 mg/day) can affect wound healing when cumulative dose is high 1

Clinical management: Continue current daily dose of glucocorticoids rather than stress dosing for patients undergoing elective surgery, but optimize by tapering to <20 mg/day prednisone when possible prior to surgery 1

Immunosuppressive Agents

Traditional immunosuppressants significantly delay wound healing:

• Mycophenolate mofetil, azathioprine, cyclosporine, and tacrolimus impair healing through leukopenia, interference with T cell costimulatory signaling, and blocking the de novo pathway of purine synthesis 1
• For patients with non-severe autoimmune disease, withhold these medications 1 week prior to surgery and restart at 3-5 days after surgery only in the absence of wound healing complications 1
• For severe SLE with organ damage, continue these medications through the surgical period due to high risk of disease flare 1

Biologic Disease-Modifying Antirheumatic Drugs (DMARDs)

Biologic agents increase infection risk and should be timed around surgical procedures:

• Restart biologic therapy only once the wound shows evidence of healing (typically ~14 days), all sutures/staples are out, there is no significant swelling, erythema, or drainage, and there is no clinical evidence of infection 1
• Tofacitinib increases risk of serious infections with incidence rate of 2.91 (95% CI 2.27-3.74) and should be withheld at least 7 days prior to surgery 1
• Bevacizumab may interfere with wound healing and carries increased risk of arterial events 1

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

NSAIDs have negative effects on wound healing and should be avoided postoperatively:

• NSAIDs suppress inflammation and fibroblast proliferation, which are critical for wound healing 4
• In experimental models, NSAIDs (diclofenac) reduced inflammation, vascularization, and number of fibroblasts compared to controls 4
• NSAIDs are among the principal drugs that can slow wound healing and should be avoided when wound healing is delayed 5
• NSAIDs used postoperatively for analgesic purposes should be avoided to prevent impaired tracheal and other wound healing 4

Anticoagulants

Anticoagulants delay wound healing through persistent bleeding and increased wound seepage:

• Anticoagulants are among the principal drugs causing delayed healing of surgical or traumatic wounds 5
• Delayed healing from anticoagulants can result in failed wound closure, deep-seated infection, and need for repeat surgery 5

Cytotoxic Antineoplastic Agents

Chemotherapy agents significantly impair wound healing:

• Cytotoxic antineoplastic agents are principal drugs that slow wound healing 5
• These agents interfere with cell proliferation necessary for tissue repair 5

Retinoids

Retinoids have mixed effects on wound healing:

• Acitretin does not significantly affect wound healing in most clinical situations, and there is no need to stop acitretin for routine surgery such as orthopedic procedures 1
• However, there is evidence that healing was delayed by retinoids in diabetic rats and that epidermal proliferation was reduced by acitretin in psoriasis 1
• In a study of 44 complex wounds in transplant recipients, there were no significant effects on wound infection, dehiscence, hypertrophic scarring, or hypergranulation 1

Clinical Approach When Wound Healing Is Delayed

When encountering delayed wound healing, systematically evaluate medication contributions:

• Consider withdrawing any drug known to impair wound healing to allow wounds to heal 5
• Monitor for signs of infection (redness, swelling, foul-smelling drainage, increased pain, fever) that require dressing removal and medical evaluation 6, 7
• Infected wounds must remain open and never be closed with sutures, staples, or adhesive to allow drainage 7
• Restart immunosuppressive or biologic therapy only after confirming adequate wound healing, typically at 14 days with no signs of infection 1