Gelcen

Gelcen is indicated for the management of neuropathic pain associated with postherpetic neuralgia.

Special Precautions

• Only physicians or health care professionals under the close supervision of a physician are to administer Gelcen.
• Use only nitrile gloves when handling Gelcen, and when cleaning capsaicin residue from the skin. Do not use latex gloves as they do not provide adequate protection.
• Immediately after use, dispose of used and unused patches, Cleansing Gel and other treatment materials in accordance with the local biomedical waste procedures.
• Use Gelcen only on dry, intact (unbroken) skin.
• Apply the Gelcen patch within 2 hours of opening the pouch.

Dosing

The recommended dose of Gelcen is a single, 60-minute application of up to four patches.

Treatment with Gelcen may be repeated every three months or as warranted by the return of pain (not more frequently than every three months).

Instructions For Use

Prepare

Put on nitrile gloves. Inspect the pouch. Do not use if the pouch has been torn or damaged.

Identify

The treatment area (painful area including areas of hypersensitivity and allodynia) must be identified by a physician and marked on the skin.

If necessary, clip hair (do not shave) in and around the identified treatment area to promote patch adherence.

Gelcen can be cut to match the size and the shape of the treatment area.

Gently wash the treatment area with mild soap and water and dry thoroughly.

Anesthetize

Pre-treat with a topical anesthetic to reduce discomfort associated with the application of Gelcen.

Apply topical anesthetic to the entire treatment area and surrounding 1 to 2 cm, and keep the local anesthetic in place until the skin is anesthetized prior to the application of Gelcen patch.

Remove the topical anesthetic with a dry wipe. Gently wash the treatment area with mild soap and water and dry thoroughly.

Apply

Tear open the pouch along the three dashed lines, remove the Gelcen patch.

Inspect the Gelcen patch and identify the outer surface backing layer with the printing on one side and the capsaicin-containing adhesive on the other side. The adhesive side of the patch is covered by a clear, unprinted, diagonally-cut release liner.

Cut Gelcen before removing the protective release liner.

The diagonal cut in the release liner is to aid in its removal. Peel a small section of the release liner back, and place the adhesive side of the patch on the treatment area.

While you slowly peel back the release liner from under the patch with one hand, use your other hand to smooth the patch down on to the skin.

Once Gelcen is applied, leave in place for 60 minutes.

To ensure Gelcen maintains contact with the treatment area, a dressing, such as rolled gauze, may be used.

Instruct the patient not to touch the patch or treatment area.

Remove

Remove Gelcen patches by gently and slowly rolling them inward.

Cleanse

After removal of Gelcen, generously apply Cleansing Gel to the treatment area and leave on for at least one minute. Remove Cleansing Gel with a dry wipe and gently wash the area with mild soap and water and dry thoroughly.

Dispose of all treatment materials as described.

Inform the patient that the treated area may be sensitive for a few days to heat (e.g., hot showers/baths, direct sunlight, vigorous exercise).

None.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Eye And Mucous Membrane Exposure

Do not apply Gelcen to the face or scalp to avoid risk of exposure to the eyes or mucous membranes.

Aerosolization Of Capsaicin

Aerosolization of capsaicin can occur upon rapid removal of Gelcen patches. Therefore, remove Gelcen patches gently and slowly by rolling the adhesive side inward.

If irritation of eyes or airways occurs, remove the affected individual from the vicinity of Gelcen. Flush eyes and mucous membranes with cool water.

Inhalation of airborne capsaicin can result in coughing or sneezing. Provide supportive medical care if shortness of breath develops.

Unintended Skin Exposure

If skin not intended to be treated comes in contact with Gelcen, apply Cleansing Gel for one minute and wipe off with dry gauze. After the Cleansing Gel has been wiped off, wash the area with soap and water.

Application Associated Pain

Even following use of a local anesthetic prior to administration of Gelcen, patients may experience substantial procedural pain. Prepare to treat acute pain during and following the application procedure with local cooling (such as an ice pack) and/or appropriate analgesic medication, such as opioids. Opioids may affect the ability to perform potentially hazardous activities such as driving or operating machinery.

Increase In Blood Pressure

In clinical trials, increases in blood pressure occurred during or shortly after exposure to Gelcen. The changes averaged less than 10 mm Hg, although some patients had greater increases and these changes lasted for approximately two hours after patch removal. Increases in blood pressure were unrelated to the pretreatment blood pressure but were related to treatment-related increases in pain. Monitor blood pressure periodically during the treatment and provide adequate support for treatment related pain.

Patients with unstable or poorly controlled hypertension, a recent history of cardiovascular or cerebrovascular events may be at an increased risk of adverse cardiovascular effects. Consider these factors prior to initiating Gelcen treatment.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Carcinogenesis

Adequate carcinogenicity studies have not been conducted with Gelcen or capsaicin.

Mutagenesis

Capsaicin was not mutagenic in the Ames, mouse micronucleus and chromosomal aberration in human peripheral blood lymphocytes assays. As with other catechol-containing compounds (e.g., dopamine), capsaicin showed a weak mutagenic response in the mouse lymphoma assay.

Impairment of Fertility

A fertility and reproductive toxicology study was conducted in rats with exposure to Gelcen patches daily for 3 hours/day beginning 28 days before cohabitation, through cohabitation and continuing through the day before sacrifice (approximately 49 days of treatment). The results revealed a statistically significant reduction in the number and percent of motile sperm. Sperm motility obtained from the vas deferens was reduced in all capsaicin treatment groups (16, 24 and 32 mg capsaicin patch/rat/day). Though a “no effect” level was not determined, dose levels used in the study correspond to a 13- to 28-fold exposure margin over the mean Cmax associated with the maximal human recommended dose. Sperm counts were reduced in the vas deferens or cauda epididymis in the 24 and 32 mg capsaicin patch/rat/day dose groups (79 and 69%, respectively) compared to the placebo patch treated control group; however, these reductions did not adversely affect fertility. As this animal model has a large excess of sperm generating capacity relative to the threshold necessary for fertilization, the lack of an effect on fertility in this species is of unknown significance for human risk assessment.

Use In Specific Populations

Pregnancy

Teratogenic effects

Pregnancy Category B

There are no adequate and well-controlled studies evaluating Gelcen in pregnant women.

There was no evidence of fetal teratogenicity in embryofetal developmental toxicological studies conducted in pregnant rats and rabbits in which Gelcen patches (rats) or liquid (rabbits) were applied once daily for a 3 hour duration during the period of fetal organogenesis up to doses corresponding to an 11-fold (rat, 32 mg capsaicin patch/day) and 37-fold (rabbit, 260 mg capsaicin/day) margin over the maximum recommended human dose [MRHD] based on a Cmax exposure comparison.

In a peri- and post-natal reproduction toxicology study, pregnant female rats were treated with Gelcen patches at doses up to 32 mg capsaicin patch/rat/day applied once daily for a 3 hours duration during gestation and lactation (from gestation day 7 through day 28 postpartum). Analyses of milk samples on day 14 of the lactation period demonstrated measurable levels of capsaicin in the dam's milk at all dose levels. There were no effects on survival, growth, learning and memory tests (passive avoidance and water maze), sexual maturation, mating, pregnancy, and fetal development in the offspring of mothers treated with capsaicin up to 32 mg capsaicin patch/rat/day (corresponding to an 11-fold margin over the MRHD based on Cmax exposure).

Labor And Delivery

The effects of Gelcen on labor and delivery are unknown.

Nursing Mothers

There are no adequate and well-controlled studies in nursing women. Studies in rat have demonstrated capsaicin is excreted into breast milk of this species. It is unknown whether capsaicin is excreted in human breast milk. Because Gelcen is administered as a single 60-minute application and capsaicin is rapidly cleared from the bloodstream , mothers can reduce infant exposure by not breast-feeding after treatment on the day of treatment.

Pediatric Use

The safety and effectiveness of Gelcen in patients younger than 18 years of age have not been studied.

Geriatric Use

In controlled clinical studies of Gelcen in neuropathic pain associated with postherpetic neuralgia, 75% of patients were 65 years and older and 43% of patients were 75 years and older.

Safety and effectiveness were similar in geriatric patients and younger patients. No dose adjustments are required in geriatric patients.

The following serious adverse reactions are discussed elsewhere in the labeling:

• Application-Associated Pain
• Increase in Blood Pressure

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of other drugs and may not reflect the rates observed in clinical practice.

Across all controlled and uncontrolled trials, more than 1,600 patients have received Gelcen. A total of 394 patients received more than one treatment application and 274 patients were followed for 48 weeks or longer.

In controlled clinical studies, 98% of patients completed ≥ 90% of the intended patch application duration. Among patients treated with Gelcen, 1% discontinued prematurely due to an adverse event.

Controlled Clinical Studies

Common Adverse Reactions

Adverse reactions occurring in ≥ 5% of patients in the Gelcen group and at an incidence greater than in the control group were application site erythema, application site pain, application site pruritus and application site papules.

Table 1 summarizes all adverse reactions, regardless of causality, occurring in ≥ 1% of patients with postherpetic neuralgia in the Gelcen group for which the incidence was greater than in the control group. The majority of application site reactions were transient and self-limited. Transient increases in pain were commonly observed on the day of treatment in patients treated with Gelcen. Pain increases occurring during patch application usually began to resolve after patch removal. On average, pain scores returned to baseline by the end of the treatment day and then remained at or below baseline levels. A majority of Gelcen-treated patients in clinical studies had adverse reactions with a maximum intensity of “mild” or “moderate”.

TABLE 1: Treatment-emergent adverse reaction incidence (%) in controlled trials in Postherpetic Neuralgia (Events in ≥ 1% of Gelcen-treated patients and at least 1% greater in the Gelcen group than in the Control group)

Other Adverse Reactions Observed During the Clinical Studies of Gelcen

General Disorders and Administration Site Conditions: Application site urticaria, Application site paresthesia, Application site dermatitis, Application site hyperesthesia, Application site excoriation, Application site warmth, Application site anesthesia, Application site bruising, Application site inflammation, Application site exfoliation, Peripheral edema

Nervous System Disorders: Headache, Burning sensation, Peripheral sensory neuropathy, Dizziness, Dysgeusia, Hyperesthesia, Hypoesthesia

Respiratory, Thoracic and Mediastinal Disorders: Cough, Throat irritation

Skin and Subcutaneous Tissue Disorders: Abnormal skin odor

There is no clinical experience with Gelcen overdose in humans.

There is no specific antidote for overdose with capsaicin. In case of suspected overdose, remove patches gently, apply Cleansing Gel for one minute, wipe off with dry gauze and gently wash the area with soap and water. Use supportive measures and treat symptoms as clinically warranted.

Two studies evaluated the pharmacodynamic effects of Gelcen on sensory function and epidermal nerve fiber (ENF) density in healthy volunteers. Consistent with the known pharmacodynamic effects of capsaicin on TRPV1-expressing nociceptive nerve endings, reduced ENF density and minor changes in cutaneous nociceptive function (heat detection and sharp sensation) were noted one week after exposure to Gelcen. ENF density reduction and sensory changes were fully reversible.

Pharmacokinetic data in humans showed transient, low ( < 5 ng/mL) systemic exposure to capsaicin in about one third of PHN patients following 60-minute applications of Gelcen. The highest plasma concentration of capsaicin detected was 4.6 ng/mL and occurred immediately after Gelcen removal. Most quantifiable levels were observed at the time of Gelcen removal and were below the limit of quantitation 3 to 6 hours after Gelcen removal. No detectable levels of metabolites were observed in any subject.