(Additions and/or revisions underlined)
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
Application-Associated
Pain
Increase
in Blood Pressure
Sensory
Function Reduction
6.1 Clinical Trials Experience
(Additions and/or revisions underlined)
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 greater than or
equal to 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.
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.
Less common adverse reactions
(<1%) with QUTENZA observed during DPN clinical trials included: dizziness,
dysesthesia, blister.
8.1 Pregnancy
(Pregnancy and Lactation Labeling
Rule (PLLR) conversion; additions and/or revisions underlined)
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 patches containing 179 mg/patch). 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.
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 patch (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 patch/day)
and 37-times (rabbit, 260 mg capsaicin/day) the MRHD based on a Cmax exposure comparison.
8.2 Lactation
(Pregnancy and Lactation Labeling
Rule (PLLR) conversion; additions and/or revisions underlined)
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. 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.
8.3
Females and Males of Reproductive Potential
(Newly added subsection)
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. 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.
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