---------------------DOSAGE FORMS AND STRENGTHS------------------­
`. Qutenza patch contains 8% capsaicin (640 mcg/cm2). Each patch
`
`contains a total of 179 mg of capsaicin. (3)
`
`---------------------------~---CONTRAIND I CA TI 0 NS-----------------------------­
`. None
`
`
`----------------------- WARNINGS AND PRECAUTIONS----------------------­
`. Do not use near eyes or mucous membranes. (5)
`
`
`. Inhalation of airborne capsaicin can result in coughing or sneezing. (5)
`
`
`. If irritation of eyes or airway occurs, remove the affected individual
`
`from the vicinity of Qutenza and flush the mucous membranes or eyes
`with water. If skin not intended to be treated comes into contact with
`with dry gauze.(5)
`Qutenza, apply Cleansing Gel and then wipe off
`
`. Transient increases in blood pressure may occur in patients during and
`
`shortly after the Qutenza treatment. Monitor blood pressure during and
`following the treatment procedure. For those patients who require the
`use of opioids to treat pain during or following the procedure, their
`abilty to perform potentially hazardous activities such as driving or
`operating machinery may be affected. (5)
`
`--------------.------------AD VERSE REA CTI ONS---------------------------.--.
`The most common adverse reactions (2: 5% and greater than control) are
`application site erythema, application site pain, application site pruritus and
`application site papules. (6.1)
`
`To report SUSPECTED ADVERSE REACTIONS, contact NeurogesX at
`1-877-900-NGSX (6479) or FDA at 1-800-FDA-1088 or
`www.fda.gov/medwatch.
`
`See Section 17 for PATIENT COUNSELING INFORMATION.
`
`Revised: November 2009
`
`17 PATIENT COUNSELING INFORMATION
`i 7. i Information for Patients
`
`· Sections or subsections omitted from the full prescribing information are not
`listed.
`
`HIGHLIGHTS OF PRESCRIBING INFORMTION
`These highlights do not include all the information needed to use
`QUTENZA safely and effectively. See full prescribing information
`for QUTENZA.
`
`QUTENZATM (capsaicin) 8% patch
`Initial U.S. Approval:
`
`---------------------------- INDICATIONS AND USA G E--------------------------­
`
`. Qutenza is a TRPV I channel agonist indicated for the management of
`
`neuropathic pain associated with postherpetic neuralgia (PHN). (I)
`
`---------------------DOSAGE AND ADMINISTRA TION---------.------------­
`. Only physicians or health care professionals under the close supervision
`
`of a physician are to administer Qutenza. (2)
`. Do not use Qutenza on broken skin. (2)
`
`. Apply Qutenza to the most painful skin areas, using up to four patches.
`(2)
`. Apply Qutenza for 60 minutes and repeat every 3 months or as
`
`warranted by the return of pain (not more frequently than every three
`months). (2)
`. Use only nitrile (not latex) gloves when handling Qutenza and when
`
`cleaning treatment areas. (2, 16)
`. Before patch application, a physician must identifY and mark the painful
`
`area, including areas of hypersensitivity and allodynia. (2)
`. Apply a topical anesthetic before Qutenza application. (2)
`
`
`. Apply Qutenza by placing on the skin while slowly removing the release
`
`liner from' underneath. (2)
`. Remove the Qutenza patches by gently and slowly rolling them inward.
`(2)
`Qutenza, apply Cleansing Gel for one minute and then
`. After removal of
`remove it with a dry wipe. (2)
`. Treat acute pain during and following the procedure with local cooling
`
`and/or analgesics. (5.4)
`. Dispose of patches and other treatment materials immediately after use
`
`in accordance with local biomedical waste procedures. (2, 16.2)
`. The treated area may be sensitive for a few days to heat (e.g., hot
`
`showerslbaths, direct sunlight, vigorous exercise). (2)
`
`FULL PRESCRIBING INFORMATION: CONTENTS*
`
`I INDICATIONS AND USAGE
`
`ADMINISTRATION
`2 DOSAGE AND
`2. i Special Precautions
`
`2.2 Dosing
`
`2.3 Instructions for Use
`
`3 DOSAGE FORMS AND STRENGTHS
`
`4 CONTRAINDICATIONS
`
`5 WARNINGS AND PRECAUTIONS
`
`5.1 Eye and Mucous Membrane Exposure
`
`5.2 Aerosolization of Capsaicin
`
`5.3 Unintended Skin Exposure
`
`5.4 Application Associated Pain and Increase in Blood Pressure
`
`6 ADVERSE REACTIONS
`
`6.1 Clinical Trials Experience
`
`7 DRUG INTERACTIONS
`
`8 USE IN SPECIFIC POPULATIONS
`
`8.1 Pregnancy
`
`8.2 Labor and Delivery
`
`8.3 Nursing Mothers
`
`8.4 Pediatric Use
`
`8.5 Geriatric Use
`
`10 OVERDOSAGE
`11 DESCRIPTION
`12 CLINICAL PHARMACOLOGY
`12. i Mechanism of Action
`12.2 Pharmacodynamics
`12.3 Pharmacokinetics
`
`13 NONCLINICAL TOXICOLOGY
`13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
`14 CLINICAL STUDIES
`
`14. i Postherpetic Neuralgia
`16 HOW SUPPLIED/STORME AND HANDLING
`16.1 Storage
`
`16.2 Handling and Di~
`
`

`

`FULL PRESCRIBING INFORMATION
`
`INDICATIONS AND USAGE
`Qutenza is indicated for the management of neuropathic pain
`associated with postherpetic neuralgia.
`
`
`2 DOSAGE AND ADMINISTRATION
`
`2. i Special Precautions
`
`
`. Only physicians or health care professionals under the close
`
`supervision of a physician are to administer Qutenza.
`. Use only nitrile gloves when handling Qutenza, 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 Cleansing Gel and
`
`other treatment materials in accordance with the local biomedical
`waste procedures.
`. Use Qutenza only on dry, intact (unbroken) skin.
`
`
`. Apply the Qutenza patch within 2 hours of opening the pouch.
`
`2.2 Dosing
`
`The recommended dose of Qutenza is a single, 60-minute application
`of up to four patches.
`Treatment with Qutenza may be repeated every three months or as
`warranted by the return of pain (not more frequently than every three
`months).
`
`2.3 lustructions for Use
`
`
`Preparation
`Put on nitrle gloves.
`
`Inspect the pouch. Do not use if the pouch has
`
`been tom 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.
`
`Ifnecessaty, clip hair (do not shave) in and
`around the identified treatment area to promote
`patch adherence.
`
`Qutenza 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
`Qutenza.
`
`Apply topical anesthetic to the entire treatment
`area and surrounding I to 2 col, and keep the
`local anesthetic in place until the skin is
`anesthetized prior to the application of Qutenza
`patch.
`
`Remove the topical anesthetic with a dr 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 Qutenza patch.
`
`Inspect the Qutenza 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 Qutenza 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 Qutenza
`is applied, leave in place for 60 minutes.
`
`To ensure Qutenza 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 Qutenza patches by gently and slowly
`rollng them inward.
`
`
`Cleanse
`After removal of Qutenza, 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
`in Section 2. i.
`
`Infono the patient that the treated area may be
`sensitive for a few days to heat (e.g., hot
`showerslbaths. direct sunlight. vigorous
`exercise).
`
`3 DOSAGE FORMS AND STRENGTHS
`
`Qutenza patch contains 8% capsaicin (640 mcg/cm2). Each patch
`
`contains a total of 179 mg of capsaicin.
`
`4 CONTRAINDICATIONS
`
`None.
`
`5 WARNINGS AND PRECAUTIONS
`
`5.1 Eye and Mucous Membrane Exposure
`
`Do not apply Qutenza to the face or scalp to avoid risk of exposure to
`the eyes or mucous membranes.
`5.2 Aerosolization of Capsaicin
`
`Aerosolization of capsaicin can occur upon rapid removal of Qutenza
`patches. Therefore, remove Qutenza patches gently and slowly by rolling
`the adhesive side inward lSee nISlrlcl;olis.!r lie (l.lJ,
`
`If irritation of eyes or airways occurs, remove the affected individual
`from the vicinity ofQutenza. Flush eyes and mucous membranes with cool
`water.
`Inhalation of airbnrni; capsaicin can result in coughing or sneezing.
`Provide sùpportive medical care if shortness of breath develops.
`5.3 Unintended Skin Exposure
`
`If skin not intended to be treated comes in contact with Qutenza,
`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.
`
`

`

`5.4 Application Associated Pain and Increase in Blood Pressure
`
`Even following use of a local anesthetic prior to administration of
`Qutenza, 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.
`In clinical trials, increases in blood pressure occurred during or
`shortly after exposure to Qutenza. 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 Qutenza treatment.
`
`6 ADVERSE REACTIONS
`
`The following serious adverse reactions are discussed elsewhere in
`the labeling:
`Application-Associated Pain (see fforliiigs oNd Preco/liiollS (5. tJ/
`Increase in Blood Pressure (see fFrllilgs oNd PrecoiiiioliS (5. tJ/
`
`6.1 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 Qutenza. 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 Qutenza,
`i % discontinued prematurely due to an adverse event.
`
`Controlled Clinical Studies
`COn/n/ON Adverse !?eoetioNs
`
`Adverse events occuring in ~ 5% of patients in the Qutenza 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 I summarizes all adverse reactions, regardless of causality,
`occurring in ~ I % of patients with postherpetic neuralgia in the Qutenza
`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 Qutenza. 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 Qutenza­
`treated patients in clinical studies had adverse reactions with a maximum
`intensity of"mild" or "moderate".
`
`TABLEt:
`Treatment.emergent adverse reaction incidence (0/0) in controlled trials in
`Postherpetic Neuralgia (Events in;a t % of Qutenza-treated patients and at
`least i % greater in the Qutenza group than in the Control group)
`
`System
`Body
`Preferred Term
`
`Qutenza
`60 minutes
`(N = 622)
`%
`
`Contröl
`60 minutes
`(N = 495)
`%
`
`GenériÎÎ Dlšo'rdersanl:1
`. M..inislralion Site Condition.
`
`Application, Site :~ryhcll~
`
`App.licatio.n ~it~ Pa!n
`
`A~plica.tion Site Pruritu~
`
`~~plication ~~.te Papule,S
`
`.
`
`.
`
`63
`
`42
`
`6
`
`6
`
`.
`
`,
`
`54
`ii
`
`4
`
`3
`
`TABLE t: (cont.)
`Treatment.emergent adverse reaction incidence (%) in controlled trials in
`Postherpetic Neuralgia (Events in:i i % of Qutenza-treated patients and at
`least i % greater in the Qutenza group than in the Control group)
`Control
`Body System
`Qutenza
`60 minutes
`60 minutes
`Prererred Term
`(N = 495)
`(N = 622)
`%
`%
`
`Application Site Edema
`
`Application Site Swelling
`
`Application Site Dryess
`
`Infections and Infestations
`
`Naso~ha.rygiti~
`
`Bronchitis
`
`Sinusitis
`
`Gastrointestinal Disorders
`
`Nausea
`
`Vomiting
`
`Skin and Subcutaneous Tissue
`
`Disorder
`
`Pruritus
`
`Vascular Disorders
`
`Hyperten~ìon.
`
`4
`
`2
`
`2
`
`4
`
`2
`
`3
`
`;
`
`3
`
`2
`
`2
`
`I
`
`I
`
`1
`
`2
`
`I
`
`I
`
`2
`
`I
`
`, I
`
`i
`
`Other Adverse Reactions Observed During the Clinical Studies or
`Qutenza
`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
`
`7 DRUG INTERACTIONS
`
`No clinical drug interaction studies have been performed.
`Data from iN vitro cytochrome P450 inhibition and induction studies
`show that capsaicin does not inhibit or induce liver cytochrome P450
`enzymes at concentrations which far exceed those measured in blood
`samples. Therefore, interactions with systemic medicinal products are
`unlikely.
`
`8 USE IN SPECIFIC POPULATIONS
`
`8. I Pregnancy
`Teratogenic erfects: Pregnancy Category B
`There are no adequate and well-controlled studies evaluating Qutenza
`in pregnant women.
`There was no evidence of fetal teratogenicity in embryofetal
`developmental toxicological studies conducted in pregnant rats and rabbits
`in which Qutenza 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 I I-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 C=x exposure comparison.
`In a peri- and post-natal reproduction toxicology study, pregnant
`female rats were treated with Qutenza 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, learing 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 II-fold margin over the
`MRHD based on C,=, exposure).
`8.2 Labor and Delivery
`The effects of Qutenza on labor and delivery are unknown.
`8.3 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 Qutenz is administered as a single 60-minute application
`and capsaicin is rapidly cleared from the bloodstream (see
`Pharmacokinetics (12.3)), mothers can reduce infant exposure by not
`breast-feeding after treatment on the day oftreatment.
`8.4 Pediatric Use
`
`The safety and effectiveness of Qutenza in patients younger than
`18 years of age have not been studied.
`8.5 Geriatric Use
`
`In controlled clinical studies of Qutenza 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.
`
`10 OVERDOSAGE
`
`There is no clinical experience with Qutenza 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.
`
`11 DESCRIPTION
`
`Qutenza (capsaicin) 8% patch contains capsaicin in a localized
`dermal delivery system. The capsaicin in Qutenza is a synthetic equivalent
`of the naturally occurring compound found in chili peppers. Capsaicin is
`soluble in alcohol, acetone, and ethyl acetate and very slightly soluble in
`water.
`Qutenza is a single-use patch stored in a foil pouch. Each Qutenza
`patch is 14 cm x 20 cm (280 cm2) and consists of a polyester backing fim
`coated with a drug-containing sil icone adhesive mixture, and covered with
`a removable polyester release liner.
`The backing fim is imprinted with "capsaicin 8%". Each Qutenz
`patch contains a total of 179 mg of capsaicin (8% in adhesive, 80 mg per
`gram of adhesive) or 640 micrograms (mcg) of capsaicin per square cm of
`patch.
`The empirical formula is C¡gH27N03, with a molecular weight of
`
`305.42. The chemical compound capsaicin ((E)-8-methyl-N-vanillyl-6­
`nonenamide) is an activating ligand for transient receptor potential
`vaniloid 1 receptor (TRPV I) and it has the following structure:
`
`FIGURE 1:
`
`Structural Formula of Capsaicin
`
`
`CI-3 0
`Órr~ ~~CI-3
`i ¿ I- CH3
`
`
`1-0
`
`The patch contains the following inactive ingredients: diethylene
`glycol monoethyl ether, dimethicone, ethyl cellulose, polyester fim,
`silicone adhesive and white ink.
`Qutenza is supplied with a Cleansing Gel which is used to remove
`residual capsaicin from the skin after treatment. Cleansing Gel consists of
`the following ingredients: butylated hydroxyanisole, carbo mer copolymer,
`edetate disodium, polyethylene glycol, purified water, and sodium
`hydroxide.
`
`12 CLINICAL PHARMACOLOGY
`12.1 Mechanism of Action
`Capsaicin is an agonist for the transient receptor potential vanilloid I
`receptor (TRPVI), which is an ion channel-receptor complex expressed on
`nociceptive nerve fibers in the skin. Topical administration of capsaicin
`causes an initial enhanced stimulation of the TRPVI -expressing cutaneous
`
`nociceptors that may be associated with painful sensations. This is
`followed by pain relief thought to be mediated by a reduction in TRPV 1­
`expressing nociceptive nerve endings (see PnornlococlIIOHlics (/.l¿;.
`
`Over the course of several months, there may be a gradual re-emergence of
`painful neuropathy thought to be due to TRPV i nerve fiber reinnervation
`of the treated area.
`12.2 Pharmacodynamics
`Two studies evaluated the pharmacodynamic effects of Qutenza on
`sensory function and epidermal nerve fiber (ENF) density in healthy
`volunteers. Consistent with the known pharmacodynamic effects of
`capsaicin on TRPV i -expressing nociceptive nerve endings, reduced ENF
`density and minor changes in cutaneous nocìceptive function (heat
`detection and sharp sensation) were noted one week after exposure to
`Qutenza. ENF density reduction and sensory changes were fully
`reversible.
`12.3 Pharmacokinetics
`Pharmacokinetic data in humans showed transient, low (-( 5 nglmL)
`systemic exposure to capsaicin in about one third of PHN patients
`following 60-minute applications of Qutenza. The highest plasma
`concentration of capsaicin detected was 4.6 nglmL and occurred
`immediately after Qutenza removaL. Most quantifiable levels were
`observed at the time of Qutenza removal and were below the limit of
`quantitation 3 to 6 hours after Qutenza removal. No detectable levels of
`metabolites were observed in any subject.
`
`CLINICAL TOXICOLOGY
`13 NON
`13.1 Carcinogenesis, Mutagenesis, Impairment of Fertilty:
`Carcinogenesis
`Adequate carcinogenicity studies have not been conducted with
`Qutenza 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 Qutenza 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 C=x
`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
`unknown
`an effect on fertility in this species is of
`
`fertilization, the lack of
`significance for human risk assessment.
`
`14 CLINICAL STUDIES
`
`14.1 Postherpetic Neuralgia
`The effcacy of Qutenza, was established in two i 2-week, double-
`blind, randomized, dose-controlled, multicenter studies. These studies
`enrolled patients with postherpetic neuralgia (PHN) persisting for at least 6
`months following healing of herpes zoster rash and a baseline score of 3-9
`on an I I-point Numerical Pain Rating Scale (NPRS) ranging from 0 (no
`pain) to 10 (worst possible pain). Qutenza and a control patch were each
`applied as a single 60-minute application. The control used in these studies
`looked similar to Qutenza but contained a low concentration of the active
`ingredient, capsaicin (3.2 mcglcm2, 0.04% w/w) to retain blinding
`regarding the known application site reactions of capsaicin (such as
`burning and erythema). The baseline mean pain scores across the 2 studies
`was approximately 6.0. Patients who entered the study on stable doses of
`pain-control medications were required to keep dosing stable throughout
`the duration of the study. Approximately half of the patients were taking
`concomitant medications including anticonvulsants, non-SSRI
`antidepressants, or opioids for their PHN at study entry. Prior to study
`patch application a topical anesthetic was applied to the treatment area for
`60 minutes. Patients were permitted to use local cool ing and additional
`analgesic medications for treatment-related discomfort as needed through
`Day 5. Patients recorded their pain daily in a diary.
`
`

`

`PHN Study I: In this 12-week study, the Qutenza group
`demonstrated a greater reduction in pain compared to the Control group
`during the primary assessment at Week 8. The percent change in average
`pain from baseline to Week 8 was - 18% (,,2%) for the low-dose control
`and -29% (,,2%) for Qutenza.
`For various degrees of improvement in pain from baseline to study
`endpoint, Figure 2 shows the fraction of patients achieving that degree of
`improvement. The figure is cumulative, so that patients whose change from
`baseline is, for example, 50%, are also included at every level of
`improvement below 50%. Patients who did not complete the study through
`Week 12 or who showed no improvement at Week 12 were assigned 0%
`improvement. Some patients experienced a decrease in pain as early as
`Week i, which persisted throughout the study. The proportion of patients
`experiencing ~ 30% reduction in pain intensity from baseline for each
`week through Week 12 is shown in Figure 3.
`
`FIGURE
`
`2:
`
`Reduction in Pain Intensity at
`Patients Achieving Various Percentages of
`Week 12 - Study 1
`
`1--=..-1
`
`~
`
`2
`
`6
`
`li
`
`i ~
`0N
`
`0
`
`o
`
`20
`
`40
`
`60
`
`80
`
`100
`
`Pecent Improvmen !r Baline
`
`
`3:
`FIGURE
`Weekly Proportion of Patients Achieving ~ 30% Pain
`Intensity Reduction - Study 1*
`
`'00
`"'
`00
`10
`
`l 00
`: 5O
`
`l 40 "
`
`::
`L. iJ
`"'
`,..
`..
`
`I
`II
`
`~
`
`e­
`
`..
`
`9 10 11' 12
`
`
`Wtlk
`
`..()nza~la.doço
`*Thc same patients may not have responded at each timepoint.
`
`PHN Study 2: In this 12-week study the Qutenza group demonstrated a
`greater reduction in pain compared to the Control group during the primary
`assessment at Week 8. The percent change in average pain from baseline to
`Week 8 was -26% (,,2%) for the low-dose control and -33% (,,2%) for
`Qutenza.
`For various degrees of improvement in pain from baseline to study
`endpoint, Figure 4 shows the fraction of patients achieving that degree of
`improvement. The figure is cumulative, so that patients whose change from
`baseline is, for example, 50%, are also included at every level of
`improvement below 50%. Patients who did not complete the study through
`Week l2 or who showed no improvement at Week 12 were assigned 0%
`improvement. Some patients eXpenced a decrease in pain as early as
`patients
`Week i, which persisted througlhe study. The proportion of
`achieving ~ 30% reduction in paiintensity from baseline for each week
`through Week 12 is shown in Fígn 5.
`
`FIGURE
`
`4:
`
`Reduction in Pain Intensity at
`
`Patients Achieviug Various Percentages of
`Week 12 - Study 2
`
`
`~
`
`2
`
`li
`
`I-_=_dl
`
`i;
`
`i ~
`0N
`
`0
`
`o
`
`40
`60
`80
`20
`Percent Improt !r Bane
`
`100
`
`5:
`FIGURE
`Weekly Proportion of Patients Achieving ~ 30% Pain
`Intensity Reduction - Study 2*
`
`'00
`"'
`00
`10
`i em
`
`l
`
`: 5O -­
`
`("
`i 40
`L. 3O
`/I
`"'
`,.. II
`..
`
`..
`
`.."..
`
`9 10 11 12
`
`
`W..k
`
`-.Qia-øIa-dco
`
`*Thc same patients may not have responded at each timepoint.
`
`16 HOW SUPPLIED/STORAGE AND HANDLING
`
`Qutenza (capsaicin) 8% patch is a single-use patch stored in a sealed
`pouch (NDC 49685-920-00).
`Each individual patch is printed with "capsaicin 8%".
`Cleansing Gel is provided in a 50 g tube.
`fll/eIZtl is tlptli/tible iii /ne .///owiJtg prese/l/tl/ioff.Y
`Carton of I patch and 50 g tube of Cleansing Gel
`(NDC 49685-920-0 I).
`Carton of2 patches and 50 g tube of Cleansing Gel
`(NDC 49685-920-02).
`16.1 Storage
`Store carton between 20° to 25°C (68° to 77°F). Excursions between
`15°C and 30°C (59°F and 86°F) are allowed.
`Keep the patch in the sealed pouch until immediately before use.
`16.2 Handling and disposal
`Qutenza contains capsaicin capable of producing severe irritation of
`eyes, skin, respiratory tract and mucous membranes. Do not dispense
`Qutenza to patients for self-administration. It is critical that health care
`professionals who administer Qutenza have completely famil iarized
`themselves with proper dosing, handling, and disposal procedures before
`handling Qutenza to avoid accidental or inadvertent capsaicin exposure to
`themselves or others (see LJostlge tliid Admiiiis/ra/ioii (.v.
`. Do not touch Qutenza, treatment areas, and all used supplies or
`
`other materials placed in contact with the treatment area without
`wearing nitrile gloves.
`. Wear nitrile gloves at all times while handling Qutenza and
`
`cleaning treatment areas. Do NOT use latex gloves.
`. Do not hold Qutenza near eyes or mucous membranes.
`
`
`

`

`. Immediately after use, dispose of used and unused patches, patch
`
`clippings, unused Cleansing Gel and associated treatment supplies
`in accordance with local biomedical waste procedures.
`
`17 PATIENT COUNSELING INFORMTION
`17.1 Information for Patients
`. Inform patients that exposure of the skin to Qutenza may result in
`
`transient erythema and burning sensation. Instruct patients not to
`touch the patch and that ifthey accidentally touch the Qutenza patch
`it may burn and/or sting.
`. Instrct patients that if irritation of eyes or airways occurs, or if any
`
`of the side effects become severe, to notifY their doctor immediately.
`. Inform patients that the treated area may be sensitive to heat (e.g., hot
`
`showerslbath, direct sunlight, vigorous exercise) for a few days
`following treatment (see Itislntcllo/ls./r Use (21)/
`
`
`. Inform patients that they may be given medication to treat acute pain
`
`these
`during and after the Qutenza application procedure. Some of
`
`medications, such as opioids, rnay affect the ability to perform
`potentially hazardous activities such as driving or operating
`machinery (see flml/lgs Q/ld PrecQllllo/ls (5)).
`. Inform patients that as a result of treatment-related increases in pain,
`small transient increases in blood pressure may occur during and
`shortly after Qutenza treatment and that blood pressure wil be
`monitored during the treatment procedure. Instruct patients to inform
`the physician ifthey have experienced any recent cardiovascular
`event (see flQnli/lgs Qlid PrecQllllo/ls (-V.
`. Instruct patients to notifY their physician if they are pregnant or breast
`
`feeding (see Use Itl S)ecljc POplIlQlitms (6' /) Q/ld (6'1)).
`
`Manufactured for NeurogesX, Inc., San Mateo, CA 94404, USA
`by Lohmann Therapie-Systeme AG (L TS), Andernach, Germany
`
`November 2009
`
`
`