6 ADVERSE REACTIONS

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

Severe Irritation Due to Accidental Exposure of Eyes, Skin, Respiratory Tract, and Mucous Membranes [see Warning and Precautions ( 5.1)]
Application-Associated Pain [see Warnings and Precautions ( 5.2)]
Increase in Blood Pressure [see Warnings and Precautions ( 5.3)]
Sensory Function Reduction [see Warning and Precautions ( 5.4)]
Severe Application Site Burns [see Warning and Precautions ( 5.5)]

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 clinical trials, 2848 patients have received QUTENZA. A total of 924 patients received more than one treatment application and 732 patients were followed for 48 weeks or longer. A total of 590 DPN patients and 1112 PHN patients have received QUTENZA across all controlled and uncontrolled clinical trials.

Among patients treated with QUTENZA, 1% discontinued prematurely due to an adverse event.

Most Common Adverse Reactions in all Controlled Clinical Trials

In all controlled clinical trials, adverse reactions occurring in ≥5% of patients in the QUTENZA group and at an incidence at least 1% greater than in the control group were application site erythema, application site pain, and application site pruritus.

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 QUTENZA application usually began to resolve after QUTENZA 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 trials had adverse reactions with a maximum intensity of "mild" or "moderate".

Postherpetic Neuralgia (PHN)

Table 1 summarizes all adverse reactions, regardless of causality, occurring in >1% of patients with PHN in the QUTENZA group for which the incidence was at least 1% greater than in the control group.

TABLE 1: Adverse Reaction Incidence (%) in Controlled Double-blind Trials in Postherpetic Neuralgia (Events in >1% of QUTENZA-treated Patients and at Least 1% Greater in the QUTENZA Group than in the Control Group)
Body System Preferred Term	QUTENZA 60 minutes (N=622) %	Control 60 minutes (N=495) %
General Disorders and Administration Site Conditions
Application site erythema	63	54
Application site pain	42	21
Application site pruritus	6	4
Application site papules	6	3
Application site edema	4	1
Application site swelling	2	1
Application site dryness	2	1
Infections and Infestations
Nasopharyngitis	4	2
Bronchitis	2	1
Sinusitis	3	1
Gastrointestinal Disorders
Nausea	5	2
Vomiting	3	1
Skin and Subcutaneous Tissue Disorder
Pruritus	2	< 1
Vascular Disorders
Hypertension	2	1

Less common adverse reactions (<1%) with QUTENZA observed during PHN clinical trials included: palpitations, tachycardia, eye pruritus, application site reactions (such as urticaria, paresthesia, dermatitis, hyperesthesia).

Neuropathic Pain Associated with Diabetic Peripheral Neuropathy (DPN)

Table 2 summarizes all adverse reactions, regardless of causality, occurring in >1% of patients with DPN in the QUTENZA group for which the incidence was at least 1% greater than in the control group.

TABLE 2: Adverse Reaction Incidence (%) in Double-blind Controlled Trials in Neuropathic Pain Associated with Diabetic Peripheral Neuropathy (Events in >1% of QUTENZA-treated Patients and at Least 1% Greater in the QUTENZA Group than in the Control Group)
Body System Preferred Term	QUTENZA 30 minutes (N=186) %	Control 30 minutes (N=183) %
General Disorders and Administration Site Conditions
Application site reactions
Burning sensation	14	3
Application site pain	10	2
Erythema	2	0
Injury, Poisoning and Procedural Complications
Excoriation	2	0
Musculoskeletal and Connective Tissue Disorders
Pain in extremity	11	6
Nervous System Disorders
Headache	3	2
Respiratory, Thoracic and Mediastinal Disorders
Upper respiratory symptoms
Upper respiratory tract infection	4	< 1
Cough	2	< 1
Vascular Disorders
Hypertension	2	< 1

Less common adverse reactions (<1%) with QUTENZA observed during DPN clinical trials included: dizziness, dysesthesia, blister.

6.2 Postmarketing Experience

Because adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The following adverse reactions have been identified during post approval use of QUTENZA: deep partial-thickness (second-degree) and full-thickness (third-degree) burns and scarring; accidental exposure (including eye pain, cough, eye and throat irritation) [see Warnings and Precautions ( 5.1, 5.5)].