Qutenza

Important Dosage and Administration Instructions

• Do not dispense QUTENZA to patients for self-administration or handling. Only physicians or healthcare professionals are to administer and handle QUTENZA.
• Unintended exposure to capsaicin can cause severe irritation of eyes, mucous membranes, respiratory tract, and skin in healthcare professionals, patients and others [see Warnings and Precautions ( 5.1)] .
• Because unintended exposure to capsaicin can cause severe irritation of eyes, mucous membranes, respiratory tract, and skin, when administering QUTENZA, it is important to follow these procedures:

   − Administer QUTENZA in a well-ventilated treatment area.
   − Wear only nitrile gloves when handling QUTENZA or any item that makes contact with QUTENZA, and when cleaning capsaicin residue from the skin. Do not use latex gloves as they do not provide adequate protection.
   − Use of a face mask and protective glasses is advisable for healthcare professionals.
   − Keep QUTENZA in the sealed pouch until immediately before use.
   − Use QUTENZA only on dry, intact (unbroken) skin.
   − In patients treated for neuropathic pain associated with diabetic peripheral neuropathy, a careful examination of the feet should be undertaken prior to each application of QUTENZA to detect skin lesions related to underlying neuropathy or vascular insufficiency. [see Warnings and Precautions ( 5.4)] .
   − During administration, avoid unnecessary contact with any items in the room, including items that the patient may later have contact with, such as horizontal surfaces and bedsheets.
   − Aerosolization of capsaicin can occur upon rapid removal of QUTENZA. Therefore, remove QUTENZA gently and slowly by rolling the adhesive side inward [see Warnings and Precautions ( 5.1)] .
   − Immediately after use, clean all areas that had contact with QUTENZA and properly dispose of QUTENZA, associated packaging, Cleansing Gel, gloves, and other treatment materials in accordance with local biomedical waste procedures.
   − If QUTENZA is cut, ensure unused pieces are properly disposed of.

Dosing

• The recommended dose of QUTENZA for neuropathic pain associated with postherpetic neuralgia is a single, 60-minute application of up to four topical systems.
• The recommended dose of QUTENZA for neuropathic pain associated with diabetic peripheral neuropathy is a single, 30-minute application on the feet of up to four topical systems.

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

Instructions for Use

USE IN NEUROPATHIC PAIN ASSOCIATED WITH POSTHERPETIC NEURALGIA (60-MINUTE APPLICATION TIME) Prepare Administer QUTENZA in a well-ventilated treatment area. Put on nitrile (not latex) gloves. Use of a face mask and protective glasses is advisable for healthcare professionals. 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 or healthcare professional and marked on the skin. If necessary, clip hair (do not shave) in and around the identified treatment area to promote QUTENZA adherence. QUTENZA can be cut to match the size and shape of the treatment area. Gently wash the treatment area with mild soap and water, and dry thoroughly. Anesthetize (optional) The treatment area may be pretreated with a topical anesthetic to potentially reduce discomfort associated with the application of QUTENZA. 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 QUTENZA. 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 and remove QUTENZA. Inspect QUTENZA 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 QUTENZA is covered by a clear, unprinted, diagonally cut release liner. Cut QUTENZA before removing the protective release liner. Ensure that unused pieces do not make contact with other objects and are disposed of appropriately. 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 QUTENZA on the treatment area. While you slowly peel back the release liner from under the QUTENZA with one hand, use your other hand to smooth QUTENZA down onto the skin. Once QUTENZA is applied, leave in place for 60 minutes (PHN). To ensure QUTENZA maintains contact with the treatment area, a dressing, such as rolled gauze, may be used. Remove the nitrile gloves after the application. Instruct the patient not to touch QUTENZA or the treatment area. Remove Put on nitrile (not latex) gloves. Remove QUTENZA by gently and slowly rolling 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. Dry thoroughly. Dispose of all treatment materials as described [see Dosage and Administration ( 2.1)] . 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).

USE IN NEUROPATHIC PAIN ASSOCIATED WITH DIABETIC PERIPHERAL NEUROPATHY (30-MINUTE APPLICATION TIME ON THE FEET) Prepare Administer QUTENZA in a well-ventilated treatment area. Put on nitrile (not latex) gloves. Use of a face mask and protective glasses is advisable for healthcare professionals. 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 or healthcare professional and marked on the skin. Examine the feet prior to application of QUTENZA to detect skin lesions related to underlying neuropathy or vascular insufficiency. If necessary, clip hair (do not shave) in and around the identified treatment area to promote QUTENZA adherence. QUTENZA can be cut to match the size and shape of the treatment area. Gently wash the treatment area with mild soap and water, and dry thoroughly. Anesthetize (optional) The treatment area may be pretreated with a topical anesthetic to potentially reduce discomfort associated with the application of QUTENZA. 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 QUTENZA. 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 and remove QUTENZA. Inspect QUTENZA 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 QUTENZA is covered by a clear, unprinted, diagonally cut release liner. Cut QUTENZA before removing the protective release liner. Ensure that unused pieces do not make contact with other objects and are disposed of appropriately. 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 QUTENZA on the treatment area. While you slowly peel back the release liner from under the QUTENZA with one hand, use your other hand to smooth QUTENZA down onto the skin. QUTENZA can be wrapped around the dorsal, lateral, and plantar surfaces of each foot to completely cover the treatment area. Once QUTENZA is applied, leave in place for 30 minutes on the feet (DPN). To ensure QUTENZA maintains contact with the treatment area, a dressing, such as rolled gauze, may be used. Remove the nitrile gloves after the application. Instruct the patient not to touch QUTENZA or the treatment area. Remove Put on nitrile (not latex) gloves. Remove QUTENZA by gently and slowly rolling 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. Dry thoroughly. Dispose of all treatment materials as described [see Dosage and Administration ( 2.1)] . 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).

Pregnancy

Risk Summary

Capsaicin is negligibly absorbed systemically following topical administration of QUTENZA, and maternal use is not expected to result in the fetal exposure to QUTENZA. In animal reproductive studies, no evidence of malformations were observed when capsaicin was administered daily by the topical route to pregnant rats and rabbits during the period of organogenesis at doses of up to 11- and 37-times, respectively, the maximum recommended human dose (MRHD) of QUTENZA at 716 mg capsaicin per day (4 topical systems containing 179 mg/topical system). In a peri- and postnatal development study, no adverse effects were observed when capsaicin was administered daily by the topical route to rats during implantation to weaning at doses of up to 11-times the MRHD (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data

Animal Data

There was no evidence of fetal malformations in embryofetal developmental toxicological studies conducted in pregnant rats and rabbits in which QUTENZA (rats) or capsaicin liquid (rabbits) were applied once daily for a 3-hour duration during the period of fetal organogenesis at doses up to 11-times (rat, 32 mg QUTENZA /day) and 37-times (rabbit, 260 mg capsaicin/day) the MRHD based on a C max exposure comparison.

In a peri- and postnatal reproduction toxicology study, pregnant female rats were treated with QUTENZA at doses up to 32 mg QUTENZA/rat/day applied once daily for a 3-hour duration during gestation and lactation (from Gestation Day 7 through Lactation Day 20). 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 QUTENZA /rat/day (11-times the MRHD based on C max exposure).

Lactation

Risk Summary
Capsaicin is negligibly absorbed systemically by the mother following topical administration of QUTENZA, and breastfeeding is not expected to result in exposure of the infant to QUTENZA [see Clinical Pharmacology ( 12.3)] . There are no data on the effects of capsaicin on milk production. To minimize potential direct exposure of QUTENZA to the breastfed infant, avoid applying QUTENZA directly to the nipple and areola.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for QUTENZA and any potential adverse effects on the breastfed infant from QUTENZA or from the underlying maternal condition.

Females and Males of Reproductive Potential

Infertility
In a fertility and reproductive toxicology study, administration of QUTENZA at 13-times the MRHD to male rats for 3 hours/day for 49 days resulted in a statistically significant reduction in the number and percent of motile sperm; however, these reductions did not adversely affect fertility [see Nonclinical Toxicology ( 13.1)] . 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 clinical significance for males of reproductive potential treated with the MRHD.

Pediatric Use

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

Geriatric Use

In controlled clinical trials 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. The safety and effectiveness were similar in geriatric patients and younger patients. No dose adjustments are required in geriatric patients.

 Severe Irritation with Unintended Capsaicin Exposure

Unintended exposure to capsaicin can cause severe irritation of eyes, mucous membranes, respiratory tract, and skin in healthcare professionals, patients, and others. Ensure that the recommended procedures and protective measures are used when administering QUTENZA [see Dosage and Administration ( 2.1)].

Eye and Mucous Membrane Exposure

• For healthcare professionals:

     ○ Wear nitrile gloves when administering QUTENZA and avoid unnecessary contact with items in the room, including items that the patient may later have contact with, such as horizontal surfaces and bedsheets.

     ○ Use of a face mask and protective glasses is advisable.

• Do not apply QUTENZA to the patient’s face, eyes, mouth, nose, or scalp to avoid risk of exposure to eyes or mucous membranes.

• Accidental exposure to the eyes and mucous membranes can occur from touching QUTENZA or items exposed to capsaicin and then touching the eyes and mucous membranes.

• If irritation of eyes or mucous membranes occurs, flush eyes and mucous membranes with cool water. Remove the affected individual (healthcare professional or patient) from the vicinity of QUTENZA.

Respiratory Tract Exposure

• Aerosolization of capsaicin can occur upon rapid removal of QUTENZA. Therefore, remove QUTENZA gently and slowly by rolling the adhesive side inward [see Dosage and Administration ( 2.1, 2.3)] .
• Inhalation of airborne capsaicin can result in coughing or sneezing. Administer QUTENZA in a well-ventilated treatment area. Provide supportive medical care if shortness of breath develops. If irritation of airways occurs, remove the affected individual (healthcare professional or patient) from the vicinity of QUTENZA. If respiratory irritation worsens or does not resolve, do not re-expose the affected healthcare professional or patient to QUTENZA [see Adverse Reactions ( 6.2)].

Skin Exposure

• If skin not intended to be treated is exposed to 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.

Thoroughly clean all areas that had contact with QUTENZA and properly dispose of QUTENZA, associated packaging, Cleansing Gel, gloves, and other treatment materials in accordance with local biomedical waste procedures [see Dosage and Administration ( 2.1, 2.3)] .

 Application-Associated Pain

Even following use of a local anesthetic prior to administration of QUTENZA, patients may experience substantial procedural pain and burning upon application of QUTENZA and following removal of QUTENZA. Prepare to treat acute pain during and following the application procedure with local cooling and/or appropriate analgesic medication.

 Increase in Blood Pressure

In clinical trials, transient 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 QUTENZA 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 and following the treatment procedure and provide adequate support for treatment-related pain.

Patients with unstable or poorly controlled hypertension, or 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.

 Sensory Function

Reductions in sensory function have been reported following administration of QUTENZA. Decreases in sensory functions are generally minor and temporary (including to thermal and other harmful stimuli). All patients with pre-existing sensory deficits should be clinically assessed for signs of sensory deterioration or loss prior to each application of QUTENZA. If sensory deterioration or loss is detected or pre-existing sensory deficit worsens, continued use of QUTENZA treatment should be reconsidered.

Severe Application Site Burns

Cases of full-thickness (third-degree) and deep partial-thickness (second-degree) burns have been reported following administration of QUTENZA. Cases of full-thickness (third-degree) burns, requiring hospitalization and skin grafting have been reported in patients who received QUTENZA for an unapproved indication and/or frequency of dosing at an application site where there had been prior skin trauma ​[see Adverse Reactions ( 6.2)]. ​Ensure that dosage and administration recommendations are followed ​[see Dosage and Administration ].​