Capsaicin - Drug Monograph

Introduction

Capsaicin is a naturally occurring alkaloid derived from plants of the genus Capsicum (chili peppers). It is the primary pungent compound responsible for the spicy sensation associated with these plants. In clinical practice, capsaicin is utilized primarily as a topical analgesic agent for various neuropathic and musculoskeletal pain conditions. It is available in multiple formulations including creams, gels, patches, and lotions in concentrations ranging from 0.025% to 8%.

Mechanism of Action

Capsaicin exerts its pharmacological effects through selective agonism of the transient receptor potential vanilloid 1 (TRPV1) receptor, a non-selective cation channel expressed on unmyelinated C-type sensory neurons. Initial application causes depolarization of nociceptive neurons, resulting in substance P release and a burning sensation. With repeated application, capsaicin induces reversible defunctionalization of nociceptive nerve endings through several mechanisms: depletion of substance P from peripheral sensory neurons, reduction of TRPV1 receptor expression, and eventual reversible retraction of epidermal nerve fibers. This leads to decreased transmission of pain signals without affecting other sensory modalities.

Indications

• FDA-approved:

- Neuropathic pain associated with postherpetic neuralgia (PHN) (8% patch) - Pain associated with diabetic peripheral neuropathy (DPN) (8% patch)

• Off-label uses:

- Osteoarthritis pain - Rheumatoid arthritis - Psoriatic arthritis - Post-surgical neuropathic pain - HIV-associated neuropathy - Pruritus - Cluster headaches (intranasal)

Dosage and Administration

• Apply to affected area 3-4 times daily
• Wash hands thoroughly after application

• Apply to most painful areas for 30-60 minutes
• May repeat every 3 months as needed
• Maximum of 4 patches per treatment session
• Pretreatment with topical anesthetic may be considered

• Renal impairment: No dosage adjustment required
• Hepatic impairment: No dosage adjustment required
• Elderly: Use with caution due to potential increased sensitivity
• Pediatric: Safety and efficacy not established

Pharmacokinetics

• Absorption: Minimal systemic absorption (<1 ng/mL plasma concentration after topical application)
• Distribution: Primarily localized to application site; negligible systemic distribution
• Metabolism: Hepatic metabolism via CYP2E1 and CYP1A2
• Elimination: Primarily renal excretion of metabolites; elimination half-life approximately 24 hours

Contraindications

• Hypersensitivity to capsaicin or any component of formulation
• Application to broken or irritated skin
• Use on face or near mucous membranes

Warnings and Precautions

• Transient burning sensation: Expected upon initial application; typically diminishes with continued use
• Hypertension risk: Transient increases in blood pressure may occur during application
• Respiratory irritation: Avoid inhalation of vapors
• Neurological effects: Rare cases of abnormal skin sensation beyond treatment area
• Cardiovascular risk: Use caution in patients with uncontrolled hypertension or recent cardiovascular events
• Skin reactions: May cause erythema, edema, or papules at application site

Drug Interactions

• ACE inhibitors: Theoretical increased risk of cough (substance P mediated)
• Topical analgesics: May alter absorption or efficacy
• Other topical products: Avoid concurrent application to same area
• CYP2E1 substrates: Potential for altered metabolism (theoretical)

Adverse Effects

• Application site erythema
• Transient burning sensation
• Pruritus
• Papules

• Application site edema
• Dry skin
• Hypertension
• Nausea

• Severe pain requiring discontinuation
• Hypersensitivity reactions
• First-degree burns (with patch)
• Abnormal skin sensation

Monitoring Parameters

• Pain assessment using validated scales (e.g., NPRS, VAS)
• Skin integrity at application sites
• Blood pressure (particularly with patch formulation)
• Patient adherence and technique of application
• Therapeutic response and need for continued therapy
• Signs of hypersensitivity reactions

Patient Education

• Expect initial burning sensation that typically decreases with repeated use
• Wash hands thoroughly after application unless treating hand pain
• Avoid contact with eyes, mucous membranes, and broken skin
• Do not apply tight bandages over treated areas
• Do not use heating pads or hot water on treated areas
• Store at room temperature away from heat and moisture
• Report severe pain, blistering, or signs of allergic reaction
• Allow skin to recover completely between patch applications
• Use exactly as prescribed; more frequent application does not enhance efficacy

References

1. Derry S, Rice AS, Cole P, et al. Topical capsaicin (high concentration) for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2017;1:CD007393.

2. FDA prescribing information for Qutenza (capsaicin) 8% patch. Revised 2020.

3. Anand P, Bley K. Topical capsaicin for pain management: therapeutic potential and mechanisms of action of the new high-concentration capsaicin 8% patch. Br J Anaesth. 2011;107(4):490-502.

4. Kennedy WR, Vanhove GF, Lu SP, et al. A randomized, controlled, open-label study of the long-term effects of NGX-4010, a high-concentration capsaicin patch, on epidermal nerve fiber density and sensory function in healthy volunteers. J Pain. 2010;11(6):579-587.

5. Mason L, Moore RA, Derry S, et al. Systematic review of topical capsaicin for the treatment of chronic pain. BMJ. 2004;328(7446):991.

6. Simpson DM, Robinson-Papp J, Van J, et al. Capsaicin 8% patch in painful diabetic peripheral neuropathy: a randomized, double-blind, placebo-controlled study. J Pain. 2017;18(1):42-53.

7. Webster LR, Peppin JF, Murphy FT, et al. Efficacy, safety, and tolerability of NGX-4010, capsaicin 8% patch, in an open-label study of patients with peripheral neuropathic pain. Diabetes Res Clin Pract. 2011;93(2):187-197.

8. Medical Economics Staff. Physicians' Desk Reference. 76th ed. Montvale, NJ: Thomson Healthcare; 2022.