- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
Excipient with known effectEach 50 g tube of cleansing gel for Qutenza contains 0.2 mg/g butylhydroxyanisole (E320).For the full list of excipients, see section 6.1.
PosologyQutenza should be applied to the most painful skin areas (using up to a maximum of 4 patches). The painful area should be determined by the physician and marked on the skin. Qutenza must be applied to intact, non-irritated, dry skin, and allowed to remain in place for 30 minutes for the feet (e.g. HIV-associated neuropathy, painful diabetic peripheral neuropathy) and 60 minutes for other locations (e.g. postherpetic neuralgia). Qutenza treatments may be repeated every 90 days, as warranted by the persistence or return of pain.The treatment area may be pre-treated with a topical anaesthetic or the patient may be administered an oral analgesic prior to application of Qutenza to reduce potential application related discomfort. The topical anaesthetic should be applied to cover the entire Qutenza treatment area and surrounding 1 to 2 cm. The topical anaesthetic or oral analgesic should be used in accordance with the medicinal product's instructions for use. In clinical trials, patients were pre-treated with topical lidocaine (4%), lidocaine (2.5%)/prilocaine (2.5%) or with 50 mg of tramadol. The anaesthetic cream should be removed prior to applying Qutenza and the skin washed and dried thoroughly.
Renal and/or hepatic impairmentNo dose adjustment is required for patients with renal or hepatic impairment.
Paediatric populationThe safety and efficacy of Qutenza in children from birth to 18 years has not been established. No data are available.
Method of administrationCutaneous use only.
Precautions to be taken before handling or administering the medicinal productNitrile gloves should be worn at all times while handling Qutenza and cleaning treatment areas. Latex gloves should NOT be worn as they do not provide adequate protection. Use of a mask and protective glasses is recommended, particularly during application and removal of the patch.These precautions should be taken to avoid unintentional contact with the patches or other materials that have come in contact with the treated areas. This may result in transient erythema and burning sensation (with mucous membranes being particularly susceptible), eye pain, eye and throat irritation and cough. Patches should not be held near eyes or mucous membranes.If necessary, hairs in the affected area should be clipped to promote patch adherence (do not shave). The treatment area(s) should be gently washed with soap and water. Following hair removal and washing, the skin should be thoroughly dried.
Instructions for useQutenza is a single use patch and can be cut to match the size and shape of the treatment area. Qutenza should be cut prior to removal of the release liner. The release liner should NOT be removed until just prior to application. There is a diagonal cut in the release liner to aid in its removal. A section of the release liner should be peeled and folded and the adhesive side of the printed patch placed on the treatment area. The patch should be held in place. The release liner should slowly and carefully be peeled from underneath with one hand while the patch should simultaneously be smoothed onto the skin with the other to ensure that there is complete contact between the patch and the skin, with no air bubbles and no moisture.When treating feet, Qutenza patches can be wrapped around the dorsal, lateral and plantar surfaces of each foot to completely cover the treatment area.To ensure Qutenza maintains contact to the treatment area, stretchable socks or rolled gauze may be used.The Qutenza patches should be removed gently and slowly by rolling them inward to minimize the risk of aerosolisation of capsaicin. After removal of Qutenza, cleansing gel should be applied liberally to the treatment area and left on for at least one minute. Cleansing gel should be wiped off with dry gauze to remove any remaining capsaicin from the skin. After the cleansing gel has been wiped off, the area should be gently washed with soap and water.Acute pain during and following the procedure should be treated with local cooling (such as a cool compress) and oral analgesics (e.g. short-acting opioids).For instructions on handling and disposal of the treatment materials see section 6.6.
Dermal assessmentQutenza should be used only on dry, intact (unbroken) skin and not on the face, above the hairline of the scalp, and/or in proximity to mucous membranes. In patients with painful diabetic peripheral neuropathy, a careful visual examination of the feet should be undertaken prior to each application of Qutenza and at subsequent clinic visits to detect skin lesions related to underlying neuropathy and vascular insufficiency.
Sensory functionReductions in sensory function have been reported following administration of Qutenza. Decreases in sensory functions are generally minor and temporary (including to thermal and sharp stimuli), however, a single case of persistent hypoesthesia has been reported in clinical studies in painful diabetic neuropathy. For this case a relationship with Qutenza could not be excluded. Caution should be exercised in patients with reduced sensation in the feet and in those at increased risk for such changes in sensory function. All patients with pre-existing sensory deficits should be clinically assessed for signs of sensory loss prior to each application of Qutenza. If sensory loss is detected or worsens, Qutenza treatment should be reconsidered.
Monitoring and management of application site reactionsApplication site reactions, such as transient local applications site burning, pain, erythema and pruritus are common or very common. In addition, there have been reported cases of burns, including second degree burns, in patients treated with capsaicin patches. See section 4.8. In patients reporting severe pain, the patch should be removed and the skin examined for chemical burn.
Unintended exposureIf Qutenza comes in contact with skin not intended to be treated, cleansing gel should be applied for one minute and wiped off with dry gauze to remove any remaining capsaicin from the skin surface. After the cleansing gel has been wiped off, the area should be gently washed with soap and water. If burning of eyes, skin, or airway occurs, the affected individual should be removed from the vicinity of Qutenza. Eyes or mucous membranes should be flushed or rinsed with water. Appropriate medical care should be provided if shortness of breath develops.
Increase in blood pressureAs a result of treatment-related increases in pain, transient increases in blood pressure (on average < 8.0 mm Hg) may occur during and shortly after the Qutenza treatment. Blood pressure should be monitored during the treatment procedure. For patients with unstable or poorly controlled hypertension or a history of cardiovascular disease, the risk of adverse cardiovascular events due to the potential stress of the procedure should be considered prior to initiating Qutenza treatment.Particular attention should be given to diabetic patients with comorbidities of coronary artery disease, hypertension and cardiovascular autonomic neuropathy.
Treatment-related discomfortPatients experiencing pain during and after patch application should be provided with supportive treatment such as local cooling or oral analgesics (i.e. short acting opioids).Patients using high doses of opioids may not respond to oral opioid analgesics when used for acute pain during and following the treatment procedure. A thorough history should be reviewed prior to initiating treatment and an alternative pain reduction strategy put in place prior to Qutenza treatment in patients with suspected high opioid tolerance.
Cleansing gelThe cleansing gel for Qutenza contains butylhydroxyanisole, which may cause local skin reactions (e.g. contact dermatitis) or irritation of the eyes and mucous membranes.
PregnancyThere are no or limited amount of data from the use of capsaicin in pregnant women. Based on human pharmacokinetics, which show transient, low systemic exposure to capsaicin, the likelihood that Qutenza increases the risk of developmental abnormalities when given to pregnant women is very low. However, caution should be exercised when prescribing to pregnant women.
Breast-feedingIt is unknown whether capsaicin/metabolites are excreted in human milk. Available pharmacodynamic/toxicological data in animals have shown excretion of capsaicin/metabolites in milk (for details see 5.3).A risk to the newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment with Qutenza.
FertilityThere is no data in humans available on fertility. A reproductive toxicology study in rats showed a reduction in the number and percent of motile sperm and the number of pregnancies (see section 5.3).
Summary of the safety profileOf the 1826 patients treated with Qutenza in randomized controlled trials, 1089 (59.6%) reported adverse reactions considered related to the medicinal product by the investigator. The most commonly reported adverse reactions were transient local application site burning, pain, erythema and pruritus. Adverse reactions were transient, self limiting and usually mild to moderate in intensity. In all controlled trials, the discontinuation rate due to adverse reactions was 2.0% for patients receiving Qutenza and 0.9% for patients receiving control.
Tabulated list of adverse reactionsIn Table 1 below all adverse reactions, which occurred at an incidence greater than control and in more than one patient in controlled clinical trials in patients with postherpetic neuralgia (PHN), painful Human Immunodeficiency Virus Associated Neuropathy (HIV-AN) and painful diabetic peripheral neuropathy, are listed by system organ class and frequency: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100) and not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.Table 1: Tabulated list of adverse reactions
|System organ class and frequency||Adverse reaction|
|Infections and infestations|
|Nervous system disorders|
|Uncommon||First degree atrio-ventricular (AV) block, tachycardia, palpitations|
|Respiratory, thoracic and mediastinal disorders|
|Uncommon||Cough, throat irritation|
|Skin and subcutaneous tissue disorders|
|Musculoskeletal and connective tissue disorders|
|Common||Pain in extremity|
|General disorders and administration site conditions|
|Very common||Application site pain, application site erythema|
|Common||Application site pruritus, application site papules, application site vesicles, application site oedema, application site swelling, application site dryness|
|Uncommon||Application site urticaria, application site paraesthesia, application site dermatitis, application site hyperaesthesia, application site inflammation, application site reaction, application site irritation, application site bruising, peripheral oedema|
|Uncommon||Increased blood pressure|
|Injury, poisoning and procedural complications|
|Not known||Burns second degree, accidental exposure (including eye pain, eye and throat irritation and cough)|
Description of selected adverse reactionsTemporary, minor changes in heat detection (1°C to 2°C) and sharp sensations were detected at the Qutenza application site in clinical trials with healthy volunteers.
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard.
Mechanism of actionCapsaicin, or 6-nonenamide, N-[(4-hydroxy-3-methoxyphenyl) methyl]-8-methyl, (6E), is a highly selective agonist for the transient receptor potential vanilloid 1 receptor (TRPV1). The initial effect of capsaicin is the activation of TRPV1-expressing cutaneous nociceptors, which results in pungency and erythema due to the release of vasoactive neuropeptides.
Pharmacodynamic effectsFollowing capsaicin exposure, cutaneous nociceptors become less sensitive to a variety of stimuli. These later-stage effects of capsaicin are frequently referred to as desensitization and are thought to underlie the pain relief. Sensations from non TRPV1-expressing cutaneous nerves are expected to remain unaltered, including the ability to detect mechanical and vibratory stimuli. Capsaicin-induced alterations in cutaneous nociceptors are reversible and it has been reported and observed that normal function (the detection of noxious sensations) returns within weeks in healthy volunteers.
Clinical efficacy and safetyEfficacy of a single 30-minute application of Qutenza to the feet has been shown in controlled clinical trials conducted in patients with painful Human Immunodeficiency Virus Associated Neuropathy (HIV-AN) and painful diabetic peripheral neuropathy. Efficacy of a single 60-minute application of Qutenza to locations other than the feet has been shown in controlled clinical trials conducted in patients with postherpetic neuralgia (PHN). Pain reduction was observed at week 1 in PHN, week 2 in HIV-AN and week 3 in painful diabetic peripheral neuropathy. For all three aetiologies efficacy was maintained throughout the 12-week study period. For painful diabetic peripheral neuropathy consistent and reproducible efficacy has been demonstrated with repeated treatments during a 52-week period. The safety profile of Qutenza in diabetic patients was consistent with that seen in the non-diabetic population.Qutenza has been shown to be effective when used alone or when used in combination with systemic medicinal products for neuropathic pain.
Matrix:silicone adhesives diethylene glycol monoethyl ethersilicone oil ethylcellulose N50 (E462)
Backing layer:polyester backing filmprinting ink containing Pigment White 6
Removable protective layer:polyester release liner
Cleansing gelmacrogol 300 carbomer purified watersodium hydroxide (E524)disodium edetatebutylhydroxyanisole (E320)
Astellas Pharma Ltd
2000 Hillswood Drive, Chertsey, Surrey, KT16 0RS, UK
+44 (0) 203 379 8820
+44 (0) 203 379 8700
0800 783 5018
+44 (0) 203 379 8721