Because everyone is sick of the stick

Because everyone is sick of the stick
SYNERA—Gives kids fast and effective needle-stick pain
prevention from a simple-to-use patch
• Prevents needle-stick pain in just 20-30 minutes1
• Proven to prevent needle-stick pain in children3
− Proven safe and effective in children as young as 3 years1
− Safe use of SYNERA in infants 4 to 6 months of age was
documented in one study1
• Simple peel-and-stick patch application that’s great for active kids
− No messy creams or ointments needed
− No need to wrap the area with a covering to keep the medications in place
INFORMATION FOR PARENTS
Because everyone
is sick of the stick
SYNERA—Gives kids fast and effective needle-stick
pain prevention from a simple-to-use patch
If you and your child
are sick of the stick…
ask your doctor or nurse
about SYNERA
In clinical studies of 1449 subjects who were given SYNERA, the most
common local reactions were redness of the skin (71%), pale skin (12%)
and swelling (12%); these reactions were generally mild and went away
on their own soon after patch removal.1
Please see complete prescribing information.
www.synera.com
Advanced relief for needle-stick grief
© 2015 Galen US Inc
PMR-DEC-2014-0349
January 2015
Advanced relief for needle-stick grief
Because everyone
is sick of the stick
SYNERA helps prevent your child’s needle-stick
pain in just 20-30 minutes1
Seeing your child sick, in pain, or uncomfortable is difficult. As a parent, you
want to do everything possible to comfort and care for your child. Sometimes
in order to help your child heal, he or she must have a needle stick for medical
tests or procedures such as blood tests or dialysis, or for delivering medication.
Fortunately, there is a simple-to-use patch called SYNERA that can help prevent
your child’s needle-stick pain.
SYNERA is indicated for use on
unbroken skin in children 3 years
and up to help prevent the pain
of needle sticks.1
SYNERA—It’s a simple-to-use patch that helps prevent your child’s
pain from needle sticks1
SYNERA is a simple-to-use patch that is placed on unbroken skin like an adhesive
bandage. The doctor or nurse simply places the SYNERA patch on your child’s skin
at the site where the needle stick will take place. SYNERA has two commonly used
numbing medications (lidocaine and tetracaine) and a gentle warming technology
that increases blood flow to the area and speeds up delivery of the numbing
medications into your child’s skin.1
SYNERA is great for active kids, because there are no messy creams or ointments
needed and your child will not need to have the area wrapped with a covering to
keep the medications in place. The SYNERA patch is simply applied to unbroken
skin, and it only takes 20-30 minutes to work.1
After 20-30 minutes, when the SYNERA patch is removed, the area will be numb
and the doctor or nurse will gently clean the area to prepare it for the needle stick.
You can trust the use of SYNERA in your child because it has been proven safe
and effective—even in children as young as 3 years of age.1
Please note, if at any time your child feels any irritation or burning, please tell
the doctor or nurse immediately.
In clinical studies of 1449 subjects who were given SYNERA, the most common
local reactions were redness of the skin (71%), pale skin (12%) and swelling
(12%); these reactions were generally mild and went away on their own soon
after patch removal.1
www.synera.com
If you and your child are sick of the stick…
ask your doctor or nurse about SYNERA
SYNERA should only be applied to healthy, unbroken skin.1
Please see complete prescribing information.
www.synera.com
Advanced relief for needle-stick grief
SYNERA—Uses a gentle warming technology to better deliver the
pain-preventing medications into the skin
• The advanced warming technology of SYNERA slightly increases
the temperature of the skin1
• Warming results in faster and better delivery of the numbing medications
into the skin
• Warming is gradual and gentle
An advanced warming technology that’s proven to help prevent pain
In a study with adults...
• SYNERA reduced pain intensity by 31% compared to a patch containing
the same numbing medications but without the warming technology2
• Significantly more subjects reported adequate pain prevention with
SYNERA2
• Significantly more subjects said they would use SYNERA for future
needle sticks2
SYNERA—It’s proven to prevent needle-stick
pain in kids
In studies with children...
• SYNERA prevented pain in significantly more patients than a patch
that contained no numbing medications3
• 59% of children aged 3 to 17 years reported no pain upon
the needle stick compared with only 20% in children who
were given a patch with no numbing medications (P<0.001)3
• Study investigators reported that 76% of children treated
with SYNERA experienced no pain compared with 20%
who were given a patch with no numbing medications (P=0.001)3
• SYNERA is proven safe and effective in children as young as
3 years of age1
• Safe use of SYNERA in infants 4 to 6 months of age
was documented in one study1
Lidocaine, one of the numbing medications in SYNERA, has been shown to
prevent the growth of viruses and bacteria. The effect of SYNERA on needle
sticks into the skin for certain vaccines has not been determined.
SYNERA is not to be used in patients with a known history of sensitivity
to the numbing medications—lidocaine and tetracaine, or topical numbing
medications of the amide or ester type, or any other component of the
product and in patients with para-aminobenzoic acid (PABA) hypersensitivity.
Please talk to your child’s doctor or nurse for more information about this.
The use of more than two SYNERA patches at the same time or one
right after the other in children is not recommended as it has not been
adequately studied.
SYNERA may lead to little or no feeling in the area of the skin where it is
applied; therefore, patients should avoid trauma (rubbing, scratching, or
exposure to heat or cold) before complete feeling returns.
Please see complete prescribing information.
www.synera.com
www.synera.com
Advanced relief for needle-stick grief
SYNERA—Faster than EMLA® at preventing needle-stick pain1,4,5
• Significantly shorter application time before procedures than EMLA®
– 20-30 minutes vs at least 1 hour1,4
If you and your child are sick of the stick…
ask your doctor or nurse about SYNERA
In a study with adults...
Significantly more subjects reported elimination
of pain with SYNERA5
SYNERA
20 min
(P=0.014)
(n=20)
60%
EMLA
SYNERA
30 min
64%
EMLA
20
95%
(P=0.020)
(n=22)
0
90%
40
60
80
100
Results from a double-blind, paired study of 82 adult volunteers randomized
to concurrently receive SYNERA and EMLA on separate antecubital surfaces
before a vascular access procedure.
SYNERA patients had more erythema (78% vs 54%); EMLA patients had
more blanching (44% vs 15%); and rates of edema were the same for both
groups (1%)5,6
More convenient than EMLA®
Application of a SYNERA topical patch
for longer than recommended, or the
application of multiple SYNERA patches
at the same time or one right after another,
could result in the absorption of enough
lidocaine and tetracaine to result in serious
adverse effects.
SYNERA should be used with caution in patients
receiving certain heart medications and/or other local pain-preventing
medications, because there may be additional toxic effects with lidocaine
and tetracaine.
SYNERA should only be applied to healthy, unbroken skin.
• Quick, simple, peel-and-stick patch application
Patients should not use SYNERA if they have a history of methemoglobinemia.
– Applies just like an adhesive bandage
• No occlusive dressing required
– Ensures no mess
• Easier for patients
– Simplifies the procedure
– Less wait time
Please see complete prescribing information.
www.synera.com
EMLA® is a registered trademark of Abraxis Bioscience, Inc.
www.synera.com
Advanced relief for needle-stick grief
SYNERA—It’s a simple-to-use patch
• SYNERA is applied to unbroken skin just
like an adhesive bandage
If you and your child are sick of the stick…
ask your doctor or nurse about SYNERA
• The package is opened, the backing
removed, and the SYNERA patch is
placed on your child’s skin in the area
where your child’s doctor or nurse
will use the needle
• Your child’s doctor or nurse will decide
the best spot for the SYNERA patch
to be placed, depending on where they
need to use the needle
• With SYNERA, there are no messy
creams or ointments needed, and your
child will not need to have the area
wrapped with a covering to keep the
medications in place
• When placed on the skin, your child will begin
to feel a gentle and gradual warming
• SYNERA raises skin temperature slightly, which
increases blood flow into the area and speeds up
delivery of the numbing medications into the skin
SYNERA should only be applied to healthy, unbroken skin.
• SYNERA prevents needle-stick pain
in just 20-30 minutes
Do not cut or remove the top cover of the patch as this could result in a burn injury.
Avoid contact of SYNERA with the eyes due to potential irritation or abrasion.
Used SYNERA patches contain a large amount of lidocaine and tetracaine (at least
90% of the initial amount). Chewing or swallowing a new or used SYNERA patch
may result in serious adverse effects. Store and dispose of SYNERA out of the
reach of children and pets.
If skin irritation or a burning sensation occurs during application, remove the patch
and inform your child’s doctor or nurse immediately.
•A
fter 20-30 minutes, the SYNERA patch
is removed
Please see complete prescribing information.
•B
efore the needle stick, the used patch is
properly disposed of away from children and pets
and the area on the skin is cleaned to prepare for
the needle stick
www.synera.com
www.synera.com
Advanced relief for needle-stick grief
IMPORTANT SAFETY INFORMATION FOR SYNERA
SYNERA has been proven safe and effective in children as young as 3 years of
age. Safe use of SYNERA in infants 4 to 6 months of age was documented in one
study. SYNERA contains medications and is only available by prescription or from
a doctor or nurse. Just like all medication prescribed by a doctor, there is important
information you should know. Please talk to your child’s doctor or nurse if you have
any questions about SYNERA.
SYNERA topical patch is only for use on healthy, unbroken skin to help prevent the
pain of needle sticks.
SYNERA is not to be used in patients with a known history of sensitivity to
lidocaine, tetracaine, numbing medications of the amide or ester type, or any other
component of the product and in patients with para-aminobenzoic acid (PABA)
hypersensitivity. Keeping a patch on longer than recommended or applying multiple
patches at the same time or one right after the other could result in absorption
of sufficient amounts of drug to result in serious adverse effects.
Patients should not use SYNERA if they have a history of methemoglobinemia.
Used SYNERA patches contain a large amount of lidocaine and tetracaine (at least
90% of the initial amount). Chewing or swallowing a new or used SYNERA patch
may result in serious adverse effects. Store and dispose of SYNERA out of the
reach of children and pets.
SYNERA should be used with caution in patients who may be more sensitive to
the general effects on the body of lidocaine and tetracaine,
particularly those who are seriously ill or weakened
by illness, and those with reduced liver function.
Patients with severe liver disease or missing
adequate blood plasma enzymes are at
greater risk of developing toxic plasma
concentrations.
Do not use on body passages such as
inside the nose or mouth or on areas
with unhealthy, broken skin.
Application to broken or inflamed
skin may result in toxic
blood concentrations
of lidocaine and
tetracaine.
narrowing of airways, and shock) to the active or inactive components of SYNERA
can occur and should be managed by a medical professional. Seek immediate
emergency help if any of these occur.
Avoid contact of SYNERA with the eyes due to potential irritation or abrasion.
If contact occurs, immediately wash out the eye with water or saline, and protect
it until sensation returns.
The application of more than two SYNERA patches at the same time or one right
after another to children is not recommended as it has not been fully studied. Safety
and effectiveness of SYNERA have been established in patients 3 years of age and
older.
Lidocaine, one of the numbing medications in SYNERA, has been shown to prevent
the growth of viruses and bacteria. The effect of SYNERA on needle sticks into the
skin for certain vaccines has not been determined.
The heating component contains iron powder, and the patch must be removed
before some diagnostic procedures, including magnetic resonance imaging (MRI).
SYNERA may lead to little or no feeling in the area of the skin where it is applied;
therefore, patients should avoid trauma (rubbing, scratching, or exposure to heat
or cold) before complete feeling returns.
SYNERA should be used with caution in patients receiving certain heart
medications and/or other local pain-preventing medications, because there may
be additional toxic effects with lidocaine and tetracaine.
In clinical studies involving 1449 subjects treated with SYNERA, the most common
local reactions were redness of the skin (71%), pale skin (12%) and swelling (12%);
these reactions were generally mild and resolved on their own soon after patch
removal. There were no treatment-related serious adverse events.1
SYNERA should be applied immediately after opening the pouch. Do not cut
or remove the top cover of the patch as this could result in a burn injury.
If skin irritation or a burning sensation occurs during application, remove the patch
and inform your child’s doctor or nurse immediately.
Please see complete prescribing information.
Allergic or extreme
sensitivity (skin rash,
swelling or hives,
www.synera.com
www.synera.com
Advanced relief for needle-stick grief
Questions often asked about SYNERA
What is SYNERA?
How long does it take SYNERA to work?
SYNERA is a technological advance which can help prevent needle-stick pain in kids
3 years of age and older. SYNERA combines two commonly used numbing medications
(lidocaine and tetracaine) with warming technology in a simple-to-use peel-and-stick
patch for certain procedures that require a needle stick. The unique warming technology
in SYNERA has been proven to enhance the anesthetic effect providing a numbing depth
of anesthesia of almost 7mm at 30 minutes, increasing to greater than 8mm even after
patch removal, greater than has been shown in separate published studies with EMLA®.7
Once placed on your child’s skin, the area will be numb in just 20-30 minutes.1
What does SYNERA look like?
SYNERA looks like a large adhesive bandage. It is oval-shaped and has SYNERA,
LIDOCAINE and TETRACAINE printed on it. There are also 6 tiny holes in the center
of the patch where the warming mechanism is located.
How big is the SYNERA patch?
The SYNERA topical patch is oval-shaped and is approximately 3-1/4 inches wide and
2-3/8 inches tall.
How does SYNERA work?
Once removed from the package and exposed to air, the SYNERA patch starts to warm
up. When placed on your child’s skin, SYNERA raises the skin temperature slightly which
increases blood flow into the area and speeds up delivery of the numbing medications
into the skin.1 After 20-30 minutes, the SYNERA patch is removed. The area will be
cleaned and your child will then be ready for the needle stick.
Does SYNERA really work?
Yes. Studies have shown that SYNERA is effective and safe to use for the prevention
of needle-stick pain—even in children as young as 3 years of age.1 In a study of children
aged 3 to 17 years, 59% of patients reported no pain upon the needle stick compared
to 20% for a patch containing no numbing medications.3 In the same study, investigators
reported that 76% of children treated with SYNERA experienced no pain compared to
20% for a patch containing no numbing medications.3
How is SYNERA applied?
SYNERA is simple to use. Once the SYNERA package is opened and the patch is
removed, it automatically begins to warm up. The backing is then removed from the
patch, and it will be applied to your child’s unbroken skin like an adhesive bandage.
It will be placed directly over the area where the needle will be inserted.
Will SYNERA hurt?
No. SYNERA should not be much different from applying or removing an adhesive
bandage. The warming is gradual and gentle. If at any time your child feels any irritation
or burning, please tell the doctor or nurse immediately.
What happens once the SYNERA patch is removed?
Once removed from the skin, the SYNERA patch is no longer delivering additional
numbing medications to your child’s skin. Gradually the normal feeling will return but
children should avoid any trauma (rubbing, scratching, or exposure to heat or cold)
before complete feeling returns to the area. Used SYNERA patches contain a large
amount of lidocaine and tetracaine. Chewing or swallowing a new or used SYNERA
patch may result in serious adverse effects. Store and dispose of SYNERA out of the
reach of children and pets.
Will my child experience any side effects with SYNERA?
In clinical studies involving 1449 subjects treated with SYNERA, the most common local
reactions were redness of the skin (71%), pale skin (12%) and swelling (12%); these
reactions were generally mild and went away on their own soon after patch removal.
There were no serious adverse events as a result of treatment with SYNERA.1
How do I get SYNERA for my child?
SYNERA can only be obtained with a prescription. Ask your child’s doctor or nurse
about getting SYNERA for your child.
How does SYNERA compare to other topical numbing creams like EMLA?
SYNERA works at least twice as fast and is more convenient to use than EMLA.1,4,5 In a
study of adults, significantly more subjects reported no pain with SYNERA after 20 and
30 minutes.5 At just 20 minutes, 90% of subjects reported no pain with SYNERA vs 60%
with EMLA, and at 30 minutes, 95% of subjects reported no pain with SYNERA vs 65%
with EMLA.5 SYNERA is more convenient to use—it takes just 20-30 minutes to work vs
at least 1 hour for EMLA.1,4 The quick and simple-to-use peel-and-stick SYNERA patch
also does not require the use of additional wraps to cover the site, making it easier and
more comfortable for patients and their parents.
Please see complete prescribing information.
www.synera.com
Advanced relief for needle-stick grief
Notes
Because everyone is sick of the stick
(Actual Size)
1. SYNERA complete prescribing information. 2. Masud S, Wasnich RD, Ruckle JL, et al. Contribution of a
heating element to topical anesthesia patch efficacy prior to vascular access: results from two randomized,
double-blind studies. J Pain Symptom Manage. 2010;40:510-519. 3. Sethna NF, Verghese ST, Hannallah
RS, Solodiuk JC, Zurakowski D, Berde CB. A randomized controlled trial to evaluate S-Caine Patch™ for
reducing pain associated with vascular access in children. Anesthesiology. 2005;102:403-408. 4. EMLA®
Cream 5% Prescribing Information. Akorn Inc., Lake Forest, IL; April 2012. 5. Sawyer J, Febbraro S, Masud
S, Ashburn MA, Campbell JC. Heated lidocaine/tetracaine patch (SYNERATM, RapydanTM) compared
with lidocaine/prilocaine cream (EMLA®) for topical anaesthesia before vascular access. Br J Anaesth.
2009;102:210-215. 6. Data on file. 7. Wallace MS, Kopecky EA, Ma T, Brophy F, Campbell JC. Evaluation
of the depth and duration of anesthesia from heated lidocaine/tetracaine (SYNERA) patches compared with
placebo patches applied to healthy adult volunteers. Reg Anesth Pain Med. 2010;35:507-513.
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AdvancedAdvanced
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Advanced relief for needle-stick grief
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information
needed to use SYNERA safely and effectively. See full
prescribing information for SYNERA.
SYNERA (lidocaine and tetracaine) topical patch
Initial U.S. Approval: 2005
INDICATIONS AND USAGE SYNERA is a combination amide and ester local
anesthetic indicated for use on intact skin to provide local
dermal analgesia for superficial venous access and
superficial dermatological procedures such as excision,
electrodessication and shave biopsy of skin lesions. (1)
Important Limitations:
• For use on intact skin only (1, 2)
• For external use only (5)
DOSAGE AND ADMINISTRATION • SYNERA should only be applied to intact skin. (2)
• Apply SYNERA for 20 to 30 minutes prior to venipuncture or
intravenous cannulation and for 30 minutes prior to
superficial dermatological procedures. (2)
5.3 Avoidance of Exposure to Eyes and Mucous
Membranes
5.4 Magnetic Resonance Imaging
5.5 Methemoglobinemia
5.6 Allergic Reactions
5.7 Special Patient Populations
5.8 Vaccinations
6  ADVERSE REACTIONS
6.1 Clinical Studies Experience
7  DRUG INTERACTIONS
7.1 Antiarrhythmic Drugs
7.2 Local Anesthetics
8  USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Labor and Delivery
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Use in Geriatric Patients
10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of
Fertility
14 CLINICAL STUDIES
14.1 Superficial Venous Access
14.2 Superficial Dermatological Procedures
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
16.2 Storage and Handling
17 PATIENT COUNSELING INFORMATION
DOSAGE FORMS AND STRENGTHS SYNERA topical patch contains 70 mg lidocaine and 70 mg
tetracaine and has an entire skin contact area of 50 cm2, of
which 10 cm2 contains lidocaine and tetracaine. (3)
*Sections or subsections omitted from the Full
Prescribing Information are not listed.
1 Indications and Usage
SYNERA is a combination amide and ester local anesthetic
indicated for use on intact skin to provide local dermal
analgesia for superficial venous access and superficial
dermatological procedures such as excision,
electrodessication and shave biopsy of skin lesions [see
Clinical Studies (14)].
CONTRAINDICATIONS • Patients with a known history of sensitivity to lidocaine,
tetracaine, or local anesthetics of the amide or ester
type. (4)
• P a t i e n t s w i t h p a r a - a m i n o b e n z o i c a c i d ( PA B A )
hypersensitivity. (4)
WARNINGS AND PRECAUTIONS • A pplication of SYNERA for longer duration than
recommended or the simultaneous or sequential application
of multiple SYNERA patches could result in serious adverse
effects. (5.1, 10)
• Store and dispose of SYNERA out of the reach of children
and pets due to the large amount of lidocaine and tetracaine
(at least 90% of the initial amount) present in used
patches. (5.2)
• Use with caution in patients who may be more sensitive to
the systemic effects of lidocaine and tetracaine, including
the acutely ill or those with severe hepatic disease or
pseudocholinesterase deficiency. (5.7)
• Allergic or anaphylactoid reactions associated with lidocaine
or tetracaine can occur. (5.6)
• Avoid contact with the eyes. (5.3)
• Not recommended for use on mucous membranes or on
areas with a compromised skin barrier. (5.3)
• The SYNERA patch must be removed before a patient
undergoes magnetic resonance imaging. (5.4)
ADVERSE REACTIONS The most common adverse reactions (>10%) were localized
and included erythema, blanching, and edema. (6)
To report SUSPECTED ADVERSE REACTIONS, contact
Galen US Inc. at 866-949-9277 and or FDA at
1-800-FDA-1088 or www.fda.gov/medwatch.
DRUG INTERACTIONS Systemic toxic effects are thought to be additive and
potentially synergistic with lidocaine and tetracaine. Use
SYNERA with caution in the following circumstances:
• in patients receiving Class I antiarrhythmic drugs (such as
tocainide and mexiletine) (7.1)
• when used concomitantly with other products containing
local anesthetic agents (7.2)
USE IN SPECIFIC POPULATIONS • Lidocaine is excreted into human milk and it is not known if
tetracaine is excreted into human milk. (8.3)
See 17 for PATIENT COUNSELING INFORMATION
Revised: March 2014
FULL PRESCRIBING INFORMATION: CONTENTS*
1 
2 
3 
4 
5 
INDICATIONS AND USAGE
DOSAGE AND ADMINISTRATION
DOSAGE FORMS AND STRENGTHS
CONTRAINDICATIONS
WARNINGS AND PRECAUTIONS
5.1 Overexposure
5.2 Storage and Disposal
FULL PRESCRIBING INFORMATION
2 Dosage and Administration
SYNERA should only be applied to intact skin. Use
immediately after opening the pouch.
For adults and children 3 years of age and older:
• Venipuncture or Intravenous Cannulation: Prior to
venipuncture or intravenous cannulation, apply
SYNERA to intact skin for 20 to 30 minutes.
• S uperficial Dermatological Procedures: For
superficial dermatological procedures such as
superficial excision or shave biopsy, apply SYNERA to
intact skin for 30 minutes prior to the procedure.
While efficacy has not been established for children less than
3 years of age, safe use of SYNERA in infants 4 to 6 months
of age was documented in one study.
Simultaneous or sequential application of multiple SYNERA
patches is not recommended. However, application of one
additional patch at a new location to facilitate venous access
is acceptable after a failed attempt. When SYNERA is used
concomitantly with other products containing local anesthetic
agents, the amount absorbed from all formulations should be
considered, as local anesthetics are thought to have at least
additive toxicities. If irritation or a burning sensation occurs
during application, remove the patch.
3 Dosage Forms and Strengths
SYNERA topical patch contains 70 mg lidocaine and 70 mg
tetracaine, has a total skin contact area of 50 cm2, and an
active drug-containing area of 10 cm2.
4Contraindications
• SYNERA is contraindicated in patients with a known
history of sensitivity to lidocaine, tetracaine, or local
anesthetics of the amide or ester type.
• SYNERA is also contraindicated in patients with paraaminobenzoic acid (PABA) hypersensitivity and in
patients with a known history of sensitivity to any other
component of the product.
5 Warnings and Precautions
5.1Overexposure
Application of a SYNERA patch for longer duration than
recommended, or the simultaneous or sequential application
of multiple SYNERA patches, could result in sufficient
absorption of lidocaine and tetracaine to result in serious
adverse effects [see Overdosage (10)].
5.2 Storage and Disposal
Used SYNERA patches contain a large amount of lidocaine
and tetracaine (at least 90% of the initial amount). The
potential exists for a child or pet to suffer serious adverse
effects from chewing or ingesting a new or used SYNERA
patch. It is important for patients to store and dispose of
SYNERA out of the reach of children and pets.
5.3Avoidance of Exposure to Eyes and Mucous
Membranes
• Contact of SYNERA with the eyes should be avoided
based on the findings of severe eye irritation with the
use of similar products in animals. Also, the loss of
protective reflexes may predispose to corneal irritation
and potential abrasion. If eye contact occurs,
immediately wash out the eye with water or saline and
protect the eye until sensation returns.
• S YNERA is not recommended for use on mucous
membranes or on areas with a compromised skin
barrier because these uses have not been studied.
Application to broken or inflamed skin may result in
toxic blood concentrations of lidocaine and tetracaine
from increased absorption.
5.4 Magnetic Resonance Imaging
The integrated heating component contains iron powder;
therefore, the SYNERA patch must be removed before a
patient undergoes magnetic resonance imaging.
5.5Methemoglobinemia
• Several local anesthetics, including tetracaine, have
been associated with methemoglobinemia. The risk of
methemoglobinemia is greatest for patients with
congenital or idiopathic methemoglobinemia, and
infants under the age of twelve months who are
receiving treatment with methemoglobin-inducing
agents.
• Very young patients or patients with glucose-6phosphate dehydrogenase deficiencies have an
increased risk of methemoglobinemia.
• Patients taking concomitant drugs associated with
drug-induced methemoglobinemia such as
sulfonamides, acetaminophen, acetanilide, aniline
dyes, benzocaine, chloroquine, dapsone, naphthalene,
nitrates and nitrites, nitrofurantoin, nitroglycerin,
nitroprusside, pamaquine, para-aminosalicylic acid,
phenacetin, phenobarbital, phenytoin, primaquine,
and quinine are also at greater risk for developing
methemoglobinemia.
• There have been no reports of methemoglobinemia
with SYNERA. However, providers are cautioned to
carefully apply SYNERA to ensure that the areas of
application and duration of application are consistent
with those recommended for the intended population.
5.6 Allergic Reactions
Allergic or anaphylactoid reactions associated with lidocaine,
tetracaine, or other components of SYNERA can occur. They
are characterized by urticaria, angioedema, bronchospasm,
and shock. If an allergic reaction occurs, it should be
managed by conventional means.
5.7 Special Patient Populations
• SYNERA should be used with caution in patients who
may be more sensitive to the systemic effects of
lidocaine and tetracaine particularly the acutely ill or
debilitated.
• P a t i e n t s w i t h s e v e r e h e p a t i c d i s e a s e o r
pseudocholinesterase deficiency, because of their
inability to metabolize local anesthetics normally, are
at a greater risk of developing toxic plasma
concentrations of lidocaine and tetracaine.
5.8Vaccinations
Lidocaine has been shown to inhibit viral and bacterial
growth. The effect of SYNERA on intradermal injections of
live vaccines has not been determined.
6 Adverse Reactions
6.1 Clinical Studies 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 another drug and may not reflect the rates
observed in clinical practice.
Three different formulations were studied during clinical
development of SYNERA: Developmental A (n=138),
Developmental B (n=30), and the SYNERA final formulation
(n=1281). The developmental patch formulations each
contained the same amount of the active drug (70 mg each of
lidocaine and tetracaine) as the final patch formulation, but
varying amounts of excipients, principally polyvinyl alcohol
and water. Data obtained from studies utilizing the
developmental patches have been included in the overall
evaluation of SYNERA safety (calculation of adverse event
incidence).
Most common adverse events in clinical trials
Localized Reactions
During or immediately after treatment with SYNERA, the skin
at the site of treatment may develop erythema, blanching,
edema, or abnormal sensation. In clinical studies involving
1449 SYNERA-treated subjects, the most common local
reactions were erythema (71%), blanching (12%) and edema
SYNERA®
(lidocaine and tetracaine) Topical Patch
(12%). These reactions were generally mild, resolving
spontaneously soon after patch removal. There were no
treatment-related serious adverse events.
Other application site reactions of various types (contact
dermatitis, rash, skin discoloration) occurred in less than 4%
of SYNERA-treated patients during clinical trials. Of these
adverse events, 75% were mild, resolving spontaneously
soon after patch removal.
Application site-related adverse events that occurred in
1% or less of SYNERA-treated subjects included rash,
pruritus, pain, contact dermatitis, infection, skin discoloration,
allergic reaction, blister, paresthesia, urticaria, and
vesiculobullous rash.
Allergic Reactions
Allergic or anaphylactoid reactions can occur with the
active or inactive components of SYNERA. They may be
characterized by urticaria, angioedema, bronchospasm, and
shock. Allergic reactions to the patch should be managed by
conventional means.
Systemic (Dose-Related) Reactions
Systemic adverse reactions that occurred in 1% or less of
SYNERA-treated subjects included dizziness, headache,
nausea, somnolence, and vomiting. Systemic adverse effects
of lidocaine and tetracaine are similar in nature to those
observed with other amide and ester local anesthetic agents,
including CNS excitation and/or depression (lightheadedness, nervousness, apprehension, euphoria,
confusion, dizziness, drowsiness, tinnitus, blurred or double
vision, vomiting, sensations of heat, cold or numbness,
twitching, tremors, convulsions, unconsciousness, respiratory
depression and arrest). Excitatory CNS reactions may be
brief or not occur at all, in which case the first manifestation
may be drowsiness merging into unconsciousness. Signs of
CNS toxicity may start at plasma concentrations of lidocaine
as low as 1000 ng/mL. The plasma concentrations at which
tetracaine toxicity may occur are less well characterized;
however, systemic toxicity with tetracaine is thought to occur
with much lower plasma concentrations compared with
lidocaine. The toxicity of co-administered local anesthetics is
thought to be at least additive. Cardiovascular manifestations
may include bradycardia, hypotension and cardiovascular
collapse leading to arrest.
7 Drug Interactions
7.1 Antiarrhythmic Drugs
SYNERA should be used with caution in patients receiving
Class I antiarrhythmic drugs (such as tocainide and
mexiletine) since the systemic toxic effects are thought to be
additive and potentially synergistic with lidocaine and
tetracaine.
7.2 Local Anesthetics
When SYNERA is used concomitantly with other products
containing local anesthetic agents, the amount absorbed
from all formulations should be considered since the systemic
toxic effects are thought to be additive and potentially
synergistic with lidocaine and tetracaine.
8 Use in Specific Populations
8.1Pregnancy
Pregnancy Category B. Lidocaine was not teratogenic in
rats given subcutaneous doses up to 60 mg/kg (360 mg/m2 or
8-fold the Single Dermal Administration (SDA)) or in rabbits
up to 15 mg/kg (180 mg/m2 or 4-fold the SDA). Tetracaine
was not teratogenic in rats given subcutaneous doses up
to 10 mg/kg (60 mg/m2 or 1-fold the SDA) or in rabbits up to
5 mg/kg (60 mg/m2 or 1-fold the SDA). SYNERA components
(lidocaine and tetracaine) given as a 1:1 eutectic mixture
were not teratogenic in rats (60 mg/m2 or 1-fold the SDA) or
rabbits (120 mg/m2 or 3-fold the SDA).
Lidocaine, contained 1:100,000 epinephrine, at a dose of
6 mg/kg (2-fold the SDA) injected into the masseter muscle
of the jaw or into the gum of the lower jaw of Long-Evans
hooded pregnant rats on Gestation Day 11 led to
developmental delays in neonatal behavior among offspring.
Developmental delays were observed for negative geotaxis,
static righting reflex, visual discrimination response,
sensitivity and response to thermal and electrical shock
stimuli, and water maze acquisition. The developmental
delays of the neonatal animals were transient with responses
becoming comparable to untreated animals later in life. The
clinical relevance of the animal data is uncertain.
Pre- and postnatal maturational, behavioral, or reproductive
development was not affected by maternal subcutaneous
administration of tetracaine during gestation and lactation up
to doses of 7.5 mg/kg (45 mg/m2 or 1-fold the SDA).
No adequate and well-controlled studies have been
conducted in pregnant women. Because animal studies are
not always predictive of human response, SYNERA should
be used during pregnancy only if the potential benefit justifies
the potential risk to the fetus.
8.2 Labor and Delivery
Neither lidocaine nor tetracaine is contraindicated in labor
and delivery. In humans, the use of lidocaine for labor
neuraxial analgesia has not been associated with an
increased incidence of adverse fetal effects either during
delivery or during the neonatal period. Tetracaine has also
been used as a neuraxial anesthetic for cesarean section
without apparent adverse effects on offspring. Should
SYNERA be used concomitantly with other products
containing lidocaine and/or tetracaine, total doses contributed
by all formulations must be considered.
8.3 Nursing Mothers
Lidocaine is excreted into human milk and it is not known if
tetracaine is excreted into human milk. Therefore, caution
should be exercised when SYNERA is administered to a
nursing mother since the milk:plasma ratio of lidocaine is 0.4
and is not determined for tetracaine. In a prior report, when
lidocaine was used as an epidural anesthetic for cesarean
section in 27 women, a milk:plasma ratio of 1.07 ±0.82
was found by using AUC values. Following single dose
administration of 20 mg of lidocaine for a dental procedure,
the point value milk: plasma ratio was similarly reported as
1.1 at five to six hours after injection. Thus, the estimated
maximum total daily dose of lidocaine delivered to the infant
via breast milk would be approximately 36 μg/kg. Based on
these data and the low concentrations of lidocaine and
tetracaine found in the plasma after topical administration of
SYNERA in recommended doses, the small amount of these
primary compounds and their metabolites that would be
ingested orally by a suckling infant is unlikely to cause
adverse effects [see Clinical Pharmacology (12.2)].
8.4 Pediatric Use
The safety and effectiveness of SYNERA have been
established in pediatric patients 3 years and older based on
adequate and well-controlled studies [see Clinical Studies
(14)]. While efficacy has not been established for children
less than 3 years of age, the safety of SYNERA in infants has
been evaluated in one study in which 34 infants 4 to 6 months
of age received SYNERA. The recommended application
time for the patch for pediatric patients is the same as for
adults. Simultaneous or sequential application of more than
two SYNERA patches to children is not recommended as it
has not been adequately studied.
8.5 Use in Geriatric Patients
In the controlled clinical studies, 139 patients over 65 years of
age, including 41 patients over 75 years of age, received
SYNERA. Visual Analog Scale (VAS) pain score differences
between SYNERA and placebo were considerably lower in
the geriatric subjects than in the rest of the adult population.
No overall differences in safety were observed between
geriatric subjects and younger subjects. However, increased
sensitivity in individual patients greater than 65 years of age
cannot be ruled out. After intravenous dosing, the elimination
half-life of lidocaine is significantly longer in elderly patients
(2.5 hours) than in younger patients (1.5 hours).
10Overdosage
In adults the maximum peak plasma concentrations of
lidocaine and tetracaine following application of two to four
SYNERA patches for 30-60 minutes were less than 9 ng/mL
and tetracaine levels were not detectable. In children, the
maximum observed peak plasma concentrations of lidocaine
were 63 ng/mL and 331 ng/mL after the application of one or
two SYNERA patches, respectively. Higher maximum
concentrations of lidocaine were observed for younger
children when compared to older children. The maximum
concentration of tetracaine observed in children was
65 ng/mL, and most values obtained were <0.9 ng/mL. Signs
of CNS toxicity may start at plasma concentrations of
lidocaine as low as 1000 ng/mL, and the risk of seizures
generally increases with increasing plasma levels.
Very high levels of lidocaine can cause respiratory arrest,
coma, decreases in cardiac output, total peripheral resistance
and mean arterial pressure, ventricular arrhythmias and
cardiac arrest. Tetracaine is associated with a profile of
systemic CNS and cardiovascular adverse events similar to
lidocaine, although toxicity associated with tetracaine is
thought to occur at lower doses compared to lidocaine. The
toxicity of co-administered local anesthetics is thought to be
at least additive. In the absence of massive topical overdose
or oral ingestion, other etiologies for the clinical effects or
overdosage from other sources of lidocaine, tetracaine or
other local anesthetics should be considered. The
management of overdosage includes close monitoring,
supportive care and symptomatic treatment. Dialysis is of
negligible value in the treatment of acute overdosage
of lidocaine.
11Description
SYNERA consists of a thin, uniform layer of a local anesthetic
formulation with an integrated, oxygen-activated heating
component that is intended to enhance the delivery of the
local anesthetic. The drug formulation is an emulsion in
which the oil phase is a eutectic mixture of lidocaine 70 mg
and tetracaine 70 mg. The eutectic mixture has a melting
point below room temperature and therefore exists as a
liquid oil rather than as crystals. The surface area of the
entire SYNERA patch is approximately 50 cm2, 10 cm2 of
which is active.
Lidocaine is chemically designated as acetamide,
2-(diethylamino)-N-(2,6-dimethylphenyl), has an
octanol:water partition ratio of 182 at pH 7.3 and has the
following structure:
Tetracaine is chemically designated as 2-(dimethylamino)
ethyl p-(butylamino)benzoate, has an octanol:water partition
ratio of 5370 at pH 7.3 and has the following structure:
Each SYNERA patch contains lidocaine 70 mg and tetracaine
70 mg in a eutectic mixture. The SYNERA formulation also
contains the following inactive ingredients: polyvinyl alcohol,
sorbitan monopalmitate, water, methylparaben and
propylparaben.
The SYNERA heating component generates a mild warming
that is intended to enhance the delivery of the local anesthetic.
SYNERA begins to heat once the patch is removed from the
pouch and is exposed to oxygen in the air. Although the patch
may increase skin temperature by up to approximately 5°C,
maximum skin temperature will not exceed 40°C. The heating
component is composed of iron powder, activated carbon,
sodium chloride, wood flour, water and filter paper.
12 Clinical Pharmacology
12.1 Mechanism of Action
SYNERA applied to intact skin provides local dermal
analgesia by the release of lidocaine and tetracaine from the
patch into the skin. Lidocaine is an amide-type local
anesthetic agent and tetracaine is an ester-type local
anesthetic agent. Both lidocaine and tetracaine block sodium
ion channels required for the initiation and conduction of
neuronal impulses, resulting in local anesthesia.
12.3Pharmacokinetics
Absorption—Application of one SYNERA patch for 30
minutes in adults produced peak plasma concentrations of
lidocaine less than 5 ng/mL while plasma levels of tetracaine
were below the limit of quantitation (<0.9 ng/mL) in all
subjects tested (n = 12, see Table 1). SYNERA application up
to 60 minutes did not significantly increase plasma levels of
lidocaine or tetracaine compared to a 30-minute application.
Table 1
Absorption of Lidocaine and Tetracaine from SYNERA
in Normal Adult Volunteers (n = 12)
Number
Age Application
of
Range
Time
SYNERA (yr)
(min)
Patches
1
18-65
30
Drug
Content
(mg)
Estimated
Cmax
Amount (ng/mL)
Absorbed
(mg)*
Tmax
(hr)
Lidocaine,
70
1.7
1.7
1.7
Tetracaine,
70
1.6
<0.9
na
*Estimated absorbed dose was calculated by subtracting the residual amount of
drug in each patch from the labeled claim.
na = not applicable
The surface area of application was 10 cm2 per Synera patch.
Application of SYNERA to broken or inflamed skin or more
than four simultaneous or sequentially applied SYNERA
patches could result in higher plasma levels of local
anesthetic that carries the risk of systemic toxicity.
Simultaneous or sequential application of multiple SYNERA
patches is not recommended. However, plasma levels of
lidocaine and tetracaine have been determined in clinical
pharmacology studies following multiple successive and
simultaneous applications of SYNERA patches on intact skin.
Maximum plasma levels of lidocaine after the application of
a) four successive SYNERA patches for 30 minutes each
with a 30-minute interval between each patch application,
and b) three SYNERA patches or 60 minutes each
with a 60-minute interval between each application were less
than 12 ng/mL and 8 ng/mL, respectively. Tetracaine was not
detected in plasma following either treatment. Simultaneous
application of two or four SYNERA patches for 60 minutes
produced peak plasma concentrations of lidocaine of less
than 9 ng/mL, while tetracaine plasma concentrations were
not detectable in all subjects (n=22). Sequential 30-minute
applications of four SYNERA patches at 60-minute intervals
SYNERA®
(lidocaine and tetracaine) Topical Patch
produced peak plasma concentrations of lidocaine of less
than 12 ng/mL, while tetracaine plasma concentrations were
below the limit of quantitation (n=11).
Distribution—When lidocaine is administered intravenously
to healthy volunteers, the steady-state volume of distribution
is approximately 0.8 to 1.3 L/kg. At lidocaine concentrations
observed following the recommended product application,
approximately 75% of lidocaine is bound to plasma proteins,
primarily alpha-1-acid glycoprotein. At much higher plasma
concentrations (1 to 4 mcg/mL of free base) the plasma
protein binding of lidocaine is concentration dependent.
Lidocaine crosses the placental and blood brain barriers,
presumably by passive diffusion. CNS toxicity is seen with
plasma levels of 5000 ng/mL of lidocaine; however a small
number of patients reportedly may show signs of toxicity at
approximately 1000 ng/mL. Volume of distribution and protein
binding have not been determined for tetracaine due to rapid
hydrolysis in plasma.
Metabolism—It is not known if lidocaine or tetracaine is
metabolized in the skin. Lidocaine is metabolized rapidly
by the liver to a number of metabolites including
monoethylglycinexylidide (MEGX) and glycinexylidide
(GX), both of which have pharmacologic activity similar to,
but less potent than that of lidocaine. The major metabolic
pathway of lidocaine, sequential N-deethylation to
monoethylglycinexylidide (MEGX) and glycinexylidide (GX),
is primarily mediated by CYP1A2 with a minor role of
CYP3A4. The metabolite, 2,6-xylidine, has unknown
pharmacologic activity. Following intravenous administration
of lidocaine, MEGX and GX concentrations in serum range
from 11% to 36% and from 5% to 11% of lidocaine
concentrations, respectively. Serum concentrations of MEGX
were about one-third the serum lidocaine concentrations.
Tetracaine undergoes rapid hydrolysis by plasma esterases.
Primary metabolites of tetracaine include para-aminobenzoic
acid and diethylaminoethanol, both of which have an
unspecified activity.
Elimination—The half-life of lidocaine elimination from the
plasma following intravenous administration is approximately
1.8 hr. Lidocaine and its metabolites are excreted by the
kidneys. More than 98% of an absorbed dose of lidocaine
can be recovered in the urine as metabolites or parent drug.
Less than 10% of lidocaine is excreted unchanged in adults,
and approximately 20% is excreted unchanged in neonates.
The systemic clearance is approximately 8-10 mL/min/kg.
During intravenous studies, the elimination half-life of
lidocaine was statistically significantly longer in elderly
patients (2.5 hours) than in younger patients (1.5 hours). The
half-life and clearance for tetracaine have not been
established for humans, but hydrolysis in the plasma is rapid.
Pediatric Patients—Application of one SYNERA patch for up
to 30 minutes in children 4 months to 12 years of age (n=18)
produced maximum peak plasma concentrations of lidocaine
and tetracaine of 63 ng/mL and 65 ng/mL, respectively.
Application of two SYNERA patches for up to 30 minutes to
children 4 months to 12 years of age (n=19) produced peak
lidocaine levels of up to 331 ng/mL and tetracaine levels of
less than 5 ng/mL.
Elderly—After application of one SYNERA patch for 20
minutes, plasma levels of lidocaine and tetracaine were
not detectable in elderly subjects (> 65 years of age, mean
72.0 ±4.3 years, n=10). After simultaneous application of
two SYNERA patches for 60 minutes to elderly subjects (> 65
years of age, mean 69.5 ±3.7 years, n=12), the maximum
peak lidocaine concentration was 6 ng/mL and tetracaine
was not detectable. During intravenous studies, the
elimination half-life of lidocaine was statistically significantly
longer in elderly patients (2.5 hours) than in younger patients
(1.5 hours).
Cardiac, Renal and Hepatic Impairment—No specific
pharmacokinetic studies were conducted. The half-life of
lidocaine may be increased in individuals with cardiac or
hepatic dysfunction. There is no established half-life for
tetracaine due to rapid hydrolysis in the plasma.
13 Nonclinical Toxicology
13.1C arcinogenesis, Mutagenesis, Impairment of
Fertility
Carcinogenesis—Long-term studies in animals have not
been performed to evaluate the carcinogenic potential of
either lidocaine or tetracaine.
Mutagenesis—The mutagenic potential of lidocaine base and
tetracaine base has been determined in the in vitro Ames
Bacterial Reverse Mutation Assay, the in vitro chromosome
aberration assay using Chinese hamster ovary cells, and the
in vivo mouse micronucleus assay. Lidocaine was negative in
all three assays. Tetracaine was negative in the in vitro Ames
assay and the in vivo mouse micronucleus assay. In the in
vitro chromosome aberration assay, tetracaine was negative
in the absence of metabolic activation, and equivocal in the
presence of metabolic activation.
Impairment of Fertility—Lidocaine did not affect fertility
in female rats when given via continuous subcutaneous
infusion via osmotic minipumps up to doses of 250 mg/kg/day
(1500 mg/m 2 or 43-fold higher than the SDA). Although
lidocaine treatment of male rats increased the copulatory
interval and lead to a dose-related decreased homogenization
resistant sperm head count, daily sperm production, and
spermatogenic efficiency, the treatment did not affect overall
fertility in male rats when given subcutaneous doses up to
60 mg/kg (360 mg/m2 or 8-fold the SDA). Tetracaine did not
affect fertility in male or female rats when given subcutaneous
doses up to 7.5 mg/kg (45 mg/m2 or 1-fold the SDA). Multiples
of exposure are based on an SDA of 70 mg each of lidocaine
and tetracaine in SYNERA patch for 30 minutes to a 60 kg
person (43 mg/m2).
14 Clinical Studies
14.1 Superficial Venous Access
Three randomized, double-blind, placebo controlled clinical
trials in adult and geriatric subjects evaluated the degree of
dermal analgesia upon venipuncture following a 20-minute
treatment with SYNERA or a placebo patch (patch with
heating component but no drug). In each trial, subjects
received SYNERA on one arm and placebo patch on the
other. In all three studies pain was measured by a 100-mm
VAS in which a lower VAS score corresponds to less pain. In
the first study in 21 subjects, median VAS scores for SYNERA
and placebo treatments were 1 mm and 9 mm, respectively.
In the second study in 40 subjects, median VAS scores were
5 mm and 28 mm for SYNERA and placebo treatments,
respectively. In the third study, in 40 subjects over the age of
65 years, median VAS scores for SYNERA and placebo
treatments were 8 mm and 14 mm, respectively.
In a randomized, double-blind, placebo controlled study, 61
pediatric patients received either SYNERA or placebo for 20
minutes prior to venipuncture or IV cannulation in the
antecubital fossa or dorsum of the hand. Subjects were
stratified by age group (3 to 6 years and 7 to 17 years).
Children in the younger group reported less pain on IV
cannulation with SYNERA than with placebo, as rated using
a six-point Oucher pain scale with faces. Children in the older
group rated their pain using an eleven-point Oucher pain
scale that contained both faces and numbers. Pain scores on
IV cannulation in the older children treated with SYNERA
were not significantly different from pain scores in those
treated with placebo.
In a double-blind trial in 250 adults, subjects were randomized
to receive either SYNERA without heating element or
SYNERA with heating element, prior to venipuncture. Median
VAS scores for the patch with the heating element and
without the heating element were 17 mm and 22 mm,
respectively.
14.2Superficial Dermatological Procedures
In one randomized, double-blind, placebo controlled study,
94 adult subjects received either SYNERA or placebo
patch for 30 minutes prior to a superficial dermatological
procedure such as superficial excision, shave biopsy or
electrodessication. Median VAS scores for SYNERA
and placebo treatments were 5 mm and 31 mm, respectively.
In a similarly designed study in 74 subjects over the age
of 65 years, less pain was reported following SYNERA
treatment compared to placebo with median VAS scores
for SYNERA and placebo treatments of 10 mm and 23 mm,
respectively.
In a randomized, double-blind, placebo controlled study, 88
pediatric patients were stratified by age group (3 to 6 years
and 7 to 17 years) to receive a 30-minute application of either
SYNERA or placebo patch, prior to lidocaine injection. In
younger children who used the Oucher pain scale with faces,
those receiving SYNERA reported less pain from lidocaine
injection than those receiving placebo. Older children used
the numerical Oucher pain scale to report pain intensity.
There was no difference between treatments observed in the
older children.
16 How Supplied/Storage and Handling
16.1How Supplied
SYNERA is available as the following:
NDC 10885-002-01 One individually packaged
SYNERA patch
NDC 10885-002-10 Box of 10 individually packaged
SYNERA patches
16.2Storage and Handling
Store at 25°C (77°F); excursions permitted to 15 to 30°C
(59 to 86°F) [see USP Controlled Room Temperature].
Keep out of reach of children and pets.
Apply SYNERA immediately upon removal from the protective
pouch.
Do not cut the patch or otherwise remove the top cover
as this could cause the patch to heat to temperatures
that could cause thermal injury. Do not cover the holes
on the top side of the patch as this could cause the patch
not to heat.
Hands should be washed after handling SYNERA, and eye
contact with SYNERA should be avoided. The used patch
should be disposed of immediately. The adhesive sides of the
patch should be folded together and the patch should then be
thrown away in a location that is out of the reach of children
and pets.
17 Patient Counseling Information
• A dvise patients to read the FDA-approved patient
labeling (Instructions for Use).
• Advise patients that SYNERA is a patch containing two
medicines (lidocaine and tetracaine) that are known as
local anesthetics, and a heating component. These
medicines are used to lessen the pain associated
with superficial venous access and superficial
dermatological procedures such as excision,
electrodessication and shave biopsy of skin lesions.
• A dvise patients that SYNERA should be applied
immediately after opening the pouch. Instruct patients
to not cut or remove the top cover of the patch as this
could result in thermal injury.
• Advise patients that keeping a patch on longer than
recommended or applying multiple patches
simultaneously or sequentially could result in systemic
absorption sufficient to result in serious adverse
effects that are typical of drugs in this class.
• Advise patients that the patch must be removed before
magnetic resonance imaging.
• Advise patients that SYNERA is contraindicated in
patients with a known history of sensitivity to lidocaine,
tetracaine, local anesthetics of the amide or ester type,
or any other component of the product and in patients
with para-aminobenzoic acid (PABA) hypersensitivity.
• Advise patients that SYNERA should be used with
caution in patients who may be more sensitive to the
systemic effects of lidocaine and tetracaine, including
the acutely ill, the debilitated, and those with
compromised hepatic function. Patients with severe
hepatic disease or pseudocholinesterase deficiency
are at greater risk of developing toxic plasma
concentrations.
• Advise patients that SYNERA should be used with
caution in patients receiving class I antiarrhythmics
and/or other local anesthetics, because the systemic
toxic effects may be additive and potentially synergistic
with lidocaine and tetracaine.
• Advise patients not to use SYNERA if they have a
history of methemoglobinemia.
• Advise patients to avoid contact of SYNERA with the
eyes due to potential irritation or abrasion. If contact
occurs, immediately wash the eye with water or saline,
and protect it until sensation returns.
• Advise patients that SYNERA should only be applied
to intact skin. Inform patients that exposure of the skin
to SYNERA may result in erythema, blanching and
edema; these reactions are generally mild, resolving
spontaneously soon after the patch is removed.
• Advise patients that SYNERA is not for use on mucous
membranes or on areas with broken skin.
• A dvise patients that if skin irritation or a burning
sensation occurs during application, the product
should be removed.
• I nform patients of the signs of an allergic or
anaphylactoid reaction (urticaria, angioedema,
bronchospasm, and shock). Instruct patients to seek
immediate emergency help if these occur.
• Advise patients that SYNERA may lead to diminished
or blocked sensation in the treated skin; therefore,
patients should avoid inadvertent trauma (rubbing,
scratching, or exposure to heat or cold) before
complete sensation returns.
• Advise patients to contact their healthcare professional
if they don’t recall where to apply the patch.
• Instruct patients to store SYNERA and to discard used
patches out of the reach of children and pets.
• The effect of SYNERA on intradermal injections of live
vaccines has not been determined.
Manufactured for: Galen US Inc.
Fretz Road
Souderton
PA 18964
Copyright Galen US Inc. © 2013
For medical information about SYNERA, call
1-866-949-9277.
WHAT THE PATCH DOES:
The medicine on this patch is used to numb the skin that it
covers. The safety and effectiveness of Synera® have been
established in adults and children 3 years of age and older.
(lidocaine and tetracaine) Topical Patch
FOLLOW THE INSTRUCTIONS BELOW,
AND THESE SAFETY TIPS:
• Do not put the patch on your lips or near your eyes.
If you get medicine from the patch in your eye, rinse your eye
with water and protect it until the numbness goes away.
INSTRUCTIONS FOR USE
• Do not cut or tear the patch.
Leave the patch in the foil pouch
until you read this leaflet
• Do not get water on the patch.
• Keep the patch away from children and pets at all times.
STEP 1:
Check the skin where the patch will be worn
• Keep the patch in the unopened foil pouch until you are ready to put it on.
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• Do not put the patch on skin that is cut, scratched or red (like a rash).
• Do not shave the area or you may hurt the skin.
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STEP 3:
Open the foil pouch and remove the patch. Save the foil pouch.
• TO TEAR OPEN THE FOIL POUCH - fold the upper right corner toward you. (See picture A)
• Press the corner flat to form a small triangle.
• Tear the foil pouch in the middle of the fold along the pre-cut slit. (See picture B)
• TO CUT OPEN WITH SCISSORS - cut carefully along
the edge of the package.
• SAVE THE FOIL POUCH.
Put the patch on your skin
• DO NOT TOUCH THE MEDICINE IN THE MIDDLE - touch only the sticky edges
of the patch. Never touch the center area.
YES
• Peel the patch off of the hard plastic backing.
• Put the sticky side of the patch on your skin, where you were told to wear it.
Press the edges to make sure the patch will stick to your skin.
• Wash your hands.
STEP 4:
NO
IMPORTANT — How to remove and discard the patch
• Do not leave the patch on the skin for longer than 30 minutes.
• Carefully peel the patch off your skin, touching only the sticky
edges of the patch - DO NOT TOUCH THE MEDICINE IN THE MIDDLE.
• PRESS THE STICKY SIDE OF THE USED PATCH ONTO THE FOIL POUCH.
• THROW FOIL POUCH WITH PATCH ATTACHED, AND HARD PLASTIC
BACKING, IN THE GARBAGE so children and pets cannot reach it.
• Wash your hands.
While wearing
the patch:
After the patch
is removed:
• Do not put the patch on your lips or near your eyes.
If you get medicine from the patch in your eye, rinse it with water until the numbness goes away.
• Do not cut or tear the patch.
• Do not get water on the patch. Keep the patch dry. Do not cover the small holes on the outside of the patch.
If you applied the patch to the back of your hand, wash your hands carefully.
• If your skin hurts or burns too much, you should take the patch off.
It is normal for the skin to feel warm, but it should not burn.
Be careful with your skin after the patch is removed. The skin that was covered by the patch stays numb
and you won’t be able to feel pain right away. Do not scratch or let this skin touch hot or cold things.
PMR-MAY-2014-0167
Date of Preparation: May 2014