Capsaicin Topical

Introduction Overview

Generic Name

capsaicin topical

Brand Name

Qutenza

Dosage Form

topical system (patches, 8%)

Drug Class

Miscellaneous topical agents

Pharmacokinetics

Absorption:
Capsaicin in Qutenza patches is applied topically and designed for localized delivery to the skin and underlying nerve fibers with minimal systemic absorption. Studies indicate that systemic absorption is very low due to the localized nature of the patch and the controlled application time (30-60 minutes) by healthcare professionals. Peak plasma concentrations are typically undetectable or negligible. This minimal systemic penetration reduces the risk of systemic side effects and drug interactions, supporting its safety profile for localized neuropathic pain management.

Distribution:
Following topical application, capsaicin binds to TRPV1 receptors on nociceptive sensory neurons in the skin. Its distribution is predominantly limited to the epidermal and dermal layers. Due to minimal systemic absorption, distribution outside the application site is negligible. Capsaicin's localization ensures targeted effects on peripheral sensory nerve endings responsible for transmitting pain signals while sparing systemic tissues, limiting unwanted effects.

Metabolism:
Metabolism of capsaicin occurs primarily in the liver when absorbed systemically, undergoing oxidative metabolism via cytochrome P450 enzymes, especially CYP2E1. However, due to negligible systemic absorption from the topical patch, hepatic metabolism is minimal in clinical use. Local enzymatic degradation at the skin level may also occur but is less well characterized. The limited systemic metabolism contributes to a limited systemic exposure and decreased potential for metabolic drug interactions.

Elimination:
Any absorbed capsaicin is excreted largely via renal clearance after hepatic metabolism into inactive metabolites. The elimination half-life of systemic capsaicin is relatively short, although this is less clinically relevant due to minimal systemic absorption from topical administration. The transient presence and rapid metabolism help minimize accumulation and systemic toxicity with repeated treatments spaced every 3 months. Local clearance at the site of application occurs through normal skin turnover and dissipation of drug residues.

Dosage Forms

Available Dosage Forms:
- Qutenza is supplied as an 8% capsaicin topical system in patch form.
- Each patch contains 179 mg of capsaicin, with a concentration of 640 mcg per cm².
- The patches are designed to be applied directly to the skin over the painful area.

Dosages for Adults and Adolescents:
- For Postherpetic Neuralgia (PHN): Up to 4 patches applied in a single session for 60 minutes.
- For Diabetic Peripheral Neuropathy (DPN) of the feet: Up to 4 patches applied in a single session for 30 minutes.
- Treatment sessions are repeated every 3 months or as clinically indicated but not more frequently.

Specific Patient Populations:
- Qutenza is approved only for adult patients; safety and efficacy in pediatric populations are not established.
- Not recommended for use on broken, irritated, or sensitive skin such as the face, scalp, or mucous membranes.
- Application requires healthcare professional administration due to the risk of local irritation and need for precise dosing.
- Special precautions should be taken in patients with uncontrolled hypertension, recent cardiovascular events, or reduced skin sensation.

Mechanism Of Action

Qutenza contains capsaicin, an active compound derived from chili peppers, which exerts its therapeutic effect primarily through interaction with the transient receptor potential vanilloid 1 (TRPV1) receptor, a non-selective cation channel expressed on nociceptive sensory neurons. Binding of capsaicin to TRPV1 results in an influx of calcium and sodium ions, leading to depolarization and activation of these pain-sensing neurons.

Upon initial activation, capsaicin induces a burning or tingling sensation, representing the excitation of sensory neurons. Continued and prolonged activation results in desensitization of these neurons, characterized by reduced responsiveness to noxious stimuli. This process involves depletion of neurotransmitters such as substance P and calcitonin gene-related peptide (CGRP), leading to diminished pain signal transmission from the peripheral nerves to the central nervous system.

Moreover, capsaicin causes reversible defunctionalization and ablation of epidermal nerve fibers through calcium overload and subsequent mitochondrial dysfunction. This neurotoxic effect leads to a prolonged decrease in pain sensation that can persist after removal of the patch, translating to extended relief of neuropathic pain symptoms.

Compared to lower concentration capsaicin creams or OTC products, Qutenza’s high 8% capsaicin concentration delivers a potent and sustained effect with longer duration of action. Clinical trials have demonstrated that this mechanism provides effective treatment for postherpetic neuralgia and diabetic peripheral neuropathy by selectively diminishing pain without systemic neurological impairment.

Pharmacological Actions

Selective agonist of TRPV1 (transient receptor potential vanilloid 1) receptors on sensory nociceptive neurons.
Induces initial excitation followed by desensitization of peripheral pain fibers.
Depletes substance P and other neuropeptides involved in pain transmission.
Causes reversible epidermal nerve fiber defunctionalization, leading to long-lasting analgesia.
Acts locally with minimal systemic absorption, reducing systemic side effects.
Provides prolonged relief of neuropathic pain symptoms such as those in postherpetic neuralgia and diabetic peripheral neuropathy.
Exhibits no central nervous system activity and thus lacks CNS-associated adverse effects common to systemic neuropathic pain treatments.
Has an irritant effect on skin that causes burning and redness at application site.
Does not alter the underlying disease process but modulates symptomatic pain transmission.
Demonstrates efficacy in reducing neuropathic pain intensity and improving quality of life in affected patients.

Therapeutic Or Clinical Uses

Treatment of postherpetic neuralgia (PHN), the persistent pain following herpes zoster (shingles) infection.
Management of neuropathic pain associated with diabetic peripheral neuropathy (DPN) in the feet.
Provides localized pain relief via topical administration without systemic side effects.
Alternative or adjunctive therapy for patients intolerant to or inadequately controlled by systemic neuropathic pain medications.
Useful in reducing the need for systemic analgesics and their associated adverse effects.
Offers prolonged pain relief lasting up to three months after a single treatment session.
Applicable for patients unable to tolerate oral or systemic neuropathic agents due to comorbidities.
May improve functional status and daily activities by reducing chronic neuropathic pain.
Can be used in cases where conventional topical analgesics provide insufficient efficacy.
Indicated for adult patients only, with administration by healthcare professionals ensuring appropriate application.

Side Or Adverse Effects

Burning sensation at the site of application, which can last from several hours up to days.
Localized pain and discomfort during and after patch application.
Erythema (redness) of the skin at the treatment site.
Pruritus (itching) and skin swelling or edema around the patch area.
Papules or skin bumps developing at or near the application site.
Dryness or peeling of the skin in the treated region.
Transient increases in blood pressure during or immediately after treatment sessions.
Headache occurring occasionally following application.
Nausea and mild systemic symptoms in rare cases due to airborne capsaicin exposure.
Coughing and sneezing due to inadvertent inhalation of capsaicin vapors during treatment.
Hypersensitivity or allergic reactions including hives, swelling, or difficulty breathing in rare cases.
Possible skin blistering or lesions if skin is overly sensitive or treatment is improperly applied.
Temporary hypoesthesia or reduced sensation of hot or sharp stimuli at the treatment site.
Irritation of mucous membranes if accidental exposure occurs to eyes, nose, or mouth.
Pain exacerbation may occur during treatment requiring local anesthetic pre-treatment.

Precautions

Qutenza patches must be applied exclusively by a qualified healthcare professional.
Avoid self-application or removal to prevent accidental exposure and irritation.
Do not apply to broken, inflamed, sunburned, scaly, or otherwise compromised skin.
Avoid contact with eyes, mucous membranes, and sensitive areas such as the face and genitals.
Caution if treating patients with poorly controlled hypertension or recent cardiovascular events.
Ensure removal of jewelry and metal objects from the treatment area prior to application.
Pre-treatment with a topical anesthetic is recommended to reduce application discomfort.
Patients should be advised to avoid touching treated skin until properly washed to prevent transfer.
Monitor blood pressure during and after application due to possible transient elevations.
Advise patients to avoid exposure of treated skin to heat sources (e.g., hot water, sun) for several days.
Use nitrile gloves during handling of patches and contaminated materials to prevent irritation.
Discontinue treatment and seek medical advice if severe pain, blistering, or persistent lesions develop.
Not recommended for use in pregnant or breastfeeding women unless clearly necessary.
Baseline assessment of skin condition and sensation is essential prior to treatment.
Avoid use in pediatric patients due to lack of established safety and efficacy.

Warnings

Risk of severe skin irritation, burns, and pain at the application site, particularly if improperly applied.
Avoid inhalation of airborne capsaicin fumes during application to prevent respiratory irritation.
Hypersensitivity reactions and allergic responses, including anaphylaxis, may occur rarely.
Not to be applied to mucous membranes, open wounds, or damaged skin due to risk of severe irritation.
Patients may experience substantial pain during treatment; adequate pre-treatment analgesia is essential.
Potential for transient increases in blood pressure necessitates monitoring, especially in high-risk cardiovascular patients.
Avoid cross-contamination to eyes or other sensitive areas during and after patch removal.
Application intervals should not be shorter than every 3 months to avoid cumulative skin damage.
Potential for respiratory distress if patch contents are inhaled accidentally, necessitating emergency measures.
Do not cover treated areas with bandages or heating devices which may intensify local skin reactions.
Use caution in patients with diminished skin sensation who may not perceive excessive burning or damage.
Risk of frostbite if cooling treatments are administered improperly post-application.
Discontinue use immediately if severe burns, blisters, or persistent erythema develop.
Loading doses should be avoided; the drug is intended for episodic application with extended action.
Qutenza is not indicated for the treatment of acute pain or inflammatory conditions beyond neuropathic etiologies.

Contraindication

Known hypersensitivity or allergy to capsaicin, chili peppers, or any component of Qutenza.
Presence of open wounds, broken, or irritated skin at the intended application site.
Use on mucous membranes including eyes, lips, nose, mouth, genitals, or rectal area is contraindicated.
Patients with severe uncontrolled hypertension or recent severe cardiovascular or cerebrovascular events.
Hypersensitivity to adhesives or excipients contained in the patch formulation.
Pediatric patients under 18 years of age due to lack of established safety and efficacy.
History of severe allergic reactions to topical analgesic agents or previous reaction to capsaicin therapy.
Patients unable to comply with application requirements or follow-up monitoring by healthcare professionals.
Contraindicated in scenarios where local skin barrier integrity is compromised by dermatologic conditions.
Not for use in pregnant or breastfeeding women unless potential benefits outweigh risks, only under medical supervision.

Drug Interactions

No significant systemic drug interactions reported due to minimal systemic absorption of capsaicin from topical application.
Concurrent use with other topical agents on the same skin area may increase local irritation and should be avoided.
Use with antihypertensive agents requires caution due to potential temporary increases in blood pressure during treatment.
No known interactions with systemic neuropathic pain medications such as pregabalin or gabapentin.
Avoid inhalation or exposure to aerosolized capsaicin with other respiratory irritants to minimize airway reactions.
Concomitant use of other topical irritants or sensitizers may potentiate local adverse reactions.
No known impact on cytochrome P450 metabolism given negligible systemic exposure.
No interactions identified with anticoagulants, antiplatelet agents, or other common cardiovascular drugs.
Potential additive effect on blood pressure if administered with systemic sympathomimetics during treatment.
No reported influence on efficacy or toxicity of vaccines or immunomodulatory agents.
No current evidence of interaction with analgesics including opioids or nonsteroidal anti-inflammatory drugs (NSAIDs).
Handling precautions are necessary to avoid inadvertent exposure to other medications or mucous membranes.
No dosage adjustment required when administered with drugs metabolized by CYP enzymes.
No data indicating interaction with herbal supplements or over-the-counter pain relief products.

Preparations Of The Drug

Qutenza is formulated as an 8% capsaicin topical patch containing 179 mg of capsaicin per patch.
Inactive ingredients include diethylene glycol monoethyl ether, dimethicone, ethyl cellulose, polyester film, silicone adhesive, and white ink.
The patch design allows controlled release and penetration of capsaicin to targeted dermal nociceptors.
Patches are applied directly to the affected area by healthcare professionals for a defined duration (30-60 minutes).
Nitrile gloves are used during handling to prevent capsaicin exposure to healthcare workers.
The product is supplied individually packaged to maintain sterility and prevent contamination.
No generic versions currently available; Qutenza is a proprietary formulation manufactured by Averitas Pharma, Inc.
Patches should be stored per manufacturer guidelines to maintain efficacy and adhesion properties.
Each patch covers a standardized area designed to deliver consistent dosing over the application period.
The 8% strength is significantly higher than OTC capsaicin creams (generally 0.025-0.1%) for enhanced efficacy.
Removal of patches after treatment is followed by immediate disposal per biohazard protocols due to capsaicin residues.
The adhesive and backing layers are engineered to minimize movement and optimize contact with the skin during treatment.
Pretreatment with a local anesthetic cream is recommended and constitutes an adjunct preparation step.
Special packaging and handling instructions to avoid accidental exposure and inhalation of capsaicin vapors.