Topical non-steroidal anti-inflammatories

Definition and Overview

Topical non-steroidal anti-inflammatory drugs (NSAIDs) are externally applied medications that deliver anti-inflammatory and analgesic effects directly to the affected tissues, such as joints, muscles, or soft tissues. Unlike their oral counterparts, topical NSAIDs provide localized relief while minimizing systemic absorption and associated adverse effects. They are especially beneficial in managing musculoskeletal pain, osteoarthritis, and soft tissue injuries, particularly in patients who are elderly or at risk for gastrointestinal, renal, or cardiovascular complications from systemic NSAIDs.

Topical NSAIDs are available in various forms including gels, creams, sprays, patches, and solutions and are widely used in both acute and chronic pain management settings.

---

Mechanism of Action

Topical NSAIDs work by inhibiting the activity of cyclooxygenase enzymes (COX-1 and COX-2) in peripheral tissues, particularly at the site of application. This inhibition leads to reduced synthesis of prostaglandins, which are chemical mediators responsible for:

• Inflammation

• Pain perception

• Edema formation

• Vasodilation

By directly delivering the active drug to the area of pain or inflammation, topical NSAIDs limit systemic distribution, thereby reducing the potential for:

• Gastrointestinal mucosal injury

• Platelet aggregation inhibition

• Renal dysfunction

• Cardiovascular risk

---

Therapeutic Indications

Topical NSAIDs are primarily indicated for the management of:

• Mild-to-moderate musculoskeletal pain

• Osteoarthritis of superficial joints (knee, hand)

• Soft tissue injuries (sprains, strains, tendinitis)

• Localized inflammatory conditions (bursitis, epicondylitis)

• Sports injuries

• Back pain (localized)

• Rheumatic conditions (limited use)

• Postoperative orthopedic pain (short-term)

---

Commonly Used Generic Topical NSAIDs

1. Diclofenac sodium / Diclofenac diethylammonium

   • Most commonly prescribed topical NSAID

   • Available as gel, patch, solution, and spray

   • Brands: Voltaren®, Pennsaid®, Solaraze®, Flector® Patch

2. Ketoprofen

   • Strong anti-inflammatory potency

   • Often used in European and Asian countries

   • Available as gel, plaster

   • Brands: Fastum®, Keplat®, Ketoflam®

3. Piroxicam

   • Used in topical gels and creams

   • Potent COX inhibitor

   • Brand examples: Feldene Gel®, Reumart®

4. Ibuprofen

   • Widely available as OTC topical gels and creams

   • Lower potency than diclofenac or ketoprofen

   • Brands: Nurofen Gel®, Ibugel®, Advil® Topical

5. Naproxen

   • Available in some compounded or over-the-counter formulations

   • Brand examples: AleveX® topical pain relief

6. Indomethacin

   • Found in compounded gels for specific inflammatory conditions

   • Limited availability as commercial topical

7. Flurbiprofen

   • Limited topical use; available as ophthalmic solution

8. Meclofenamate and Etofenamate

   • Available in certain regions (mainly Europe and Asia)

   • Etofenamate is a flufenamic acid derivative in topical formulations

---

Formulations and Administration

• Gels and creams: Most common form; applied with massage into affected area

• Solutions: Liquid forms like diclofenac solution (Pennsaid®) used for osteoarthritis

• Patches: Provide sustained release (e.g., Flector® Patch)

• Sprays and foams: For ease of application on larger or difficult-to-reach areas

Dosing Frequency:

• Typically 2 to 4 times daily depending on the product

• Duration: Use for up to 14 days for acute pain and up to 12 weeks for osteoarthritis depending on the agent

---

Pharmacokinetics

• Absorption: Generally low systemic absorption (<10% compared to oral)

• Onset of action: 15–60 minutes for pain relief

• Duration: Typically 4–6 hours per application

• Factors affecting absorption:

  • Skin integrity (intact vs broken)

  • Area of application

  • Occlusion (may increase absorption)

  • Age (children/elderly have more permeable skin)

---

Advantages Over Oral NSAIDs

• Reduced risk of gastrointestinal bleeding and ulcers

• Lower incidence of renal toxicity

• Negligible cardiovascular risk

• Targeted relief without systemic burden

• Improved patient compliance in elderly or polymedicated patients

---

Adverse Effects

1. Local Reactions:

   • Dermatitis (irritant or allergic)

   • Erythema

   • Pruritus

   • Rash

   • Photosensitivity (especially ketoprofen)

   • Dryness or peeling

   • Contact urticaria

2. Systemic Effects (rare):

   • Hypersensitivity reactions

   • Renal dysfunction (only with prolonged or high-dose use)

   • NSAID-induced asthma exacerbation (in sensitive individuals)

3. Photosensitivity:

   • Especially common with ketoprofen

   • Avoid sunlight for several days after application

---

Contraindications

• Known hypersensitivity to NSAIDs

• History of aspirin-exacerbated respiratory disease (AERD)

• Active skin disease or dermatitis at site of application

• Broken or damaged skin

• Use in children under 12 years (some products)

• Concurrent systemic NSAID use (relative contraindication if overexposure risk)

---

Precautions

• Avoid applying to mucous membranes or eyes

• Avoid occlusive dressings unless advised

• Avoid excessive sunlight or UV exposure (especially with ketoprofen)

• Use lowest effective dose for shortest duration

• Monitor for skin reactions during prolonged use

• Wash hands after application

---

Drug Interactions

While topical NSAIDs have minimal systemic exposure, the following are notable:

• Oral NSAIDs or aspirin: May increase total NSAID exposure, raising risk of GI, renal, or CV toxicity

• Warfarin and other anticoagulants: Theoretical interaction risk if significant systemic absorption occurs

• Methotrexate: Monitor in patients using high doses concurrently

• Photosensitizing medications: Caution with ketoprofen use

---

Special Populations

• Elderly: Preferred route due to reduced systemic risks

• Pregnancy: Avoid in third trimester; use caution in 1st and 2nd trimester

• Lactation: Limited data; small quantities over intact skin considered low risk

• Pediatrics: Most products not approved for children under 12 without physician supervision

---

Monitoring Parameters

• Symptom relief (pain and swelling)

• Tolerability of skin

• Signs of local hypersensitivity or photosensitivity

• Assess for signs of unintentional systemic effects (in long-term use)

---

Patient Counseling Points

• Apply only to intact, clean, dry skin

• Do not cover with tight bandages or apply heat after application

• Do not apply near eyes, nose, mouth, or genitals

• Avoid sunlight on the application site

• Discontinue use if rash, burning, or blistering occurs

• Store away from direct heat and light

• Inform healthcare provider if pain persists after 7–14 days of use

---

Clinical Guidelines and Evidence

• NICE guidelines: Recommend topical NSAIDs as first-line treatment for knee or hand osteoarthritis

• OARSI 2019: Endorse topical NSAIDs as preferred agents in elderly patients with localized OA

• Cochrane Reviews: Moderate-to-high quality evidence shows topical diclofenac is effective in chronic musculoskeletal pain

• American College of Rheumatology (ACR): Strongly recommends topical NSAIDs for initial therapy in hand/knee OA

---

Commercially Available Topical NSAID Products

Product Name	Active Ingredient	Form
Voltaren Gel	Diclofenac sodium 1%	Gel
Pennsaid	Diclofenac sodium 1.5%/2%	Topical solution
Flector Patch	Diclofenac epolamine 1.3%	Medicated patch
Nurofen Gel	Ibuprofen 5%	Gel
Fastum Gel	Ketoprofen 2.5%	Gel
AleveX	Naproxen-based (US only)	Gel
Solaraze Gel	Diclofenac 3%	Gel (also used for actinic keratosis)