Approved Drug Label (PDF)
Boxed Warning
Additions
and/or revisions underlined:
WARNING: RISK OF
SERIOUS CARDIOVASCULAR EVENTS AND GASTROINTESTINAL EVENTS
See
full prescribing information for complete boxed warning
Nonsteroidal
anti-inflammatory drugs (NSAIDs) cause an increased risk of serious
cardiovascular thrombotic events, including myocardial infarction and stroke,
which can be fatal. This risk may occur early in treatment and may increase
with duration of use. (5.4)
SOLARAZE is
contraindicated in the setting of coronary artery bypass graft (CABG) surgery.
(4, 5.4)
NSAIDs
cause an increased risk of serious gastrointestinal (GI) adverse events
including bleeding, ulceration, and perforation of the stomach or intestines,
which can be fatal. These events can occur at any time during use and without
warning symptoms. Elderly patients and patients with a prior history of peptic
ulcer disease and/or GI bleeding are at greater risk for serious GI events
(5.5)
4
Contraindications
Solaraze
is contraindicated in the following patients:
With known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to diclofenac or any
components of the drug product [see
Warnings and Precautions (5.1, 5.3) and Description (11)]
With the history of asthma, urticaria, or other allergic
type reactions after
taking aspirin or other NSAIDs.
Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been
reported in such patients [see Warnings
and Precautions (5.1, 5.2)]
Application on damaged skin resulting from any etiology, including exudative dermatitis, eczema, infected
lesions, burns or wounds [see Warnings
and Precautions (5.3)]
In the setting of coronary bypass
graft (CABG) surgery
[see Warnings and Precautions (5.4)]
5
Warnings and Precautions
PLR
conversion; newly created subsections as below.
See label for complete information.
5.1
Anaphylactic Reactions
5.2
Exacerabation of Asthma Related to Aspirin Sensitivity
5.3
Serious Skin Reactions
5.4
Cardiovascular Thrombotic Events
5.5
Gastrointestinal Bleeding, Ulceration, and Perforation
5.6
Hepatotoxicity
5.7
Hypertension
5.8
Heart Failure and Edema
5.9
Renal Toxicity and Hyperkalemia
5.10
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
5.11
Toxicity
5.12
Hematologic Toxicity
5.13
Masking of Inflammation and Fever
5.14
Laboratory Monitoring
5.15
Photosensitivity
5.16
Exposure to Eyes and Mucosal Membranes
5.17
Oral Nonsteroidal Anti-Inflammatory Drugs
6
Adverse Reactions
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listing:
The following
adverse reactions are discussed in greater detail
in other sections
of the labeling:
Anaphylactic Reactions
[see Warnings and Precautions (5.1)]
Exacerbation of Asthma Related
to Aspirin Sensitivity [see Warnings
and Precautions (5.2)]
Serious Skin Reactions [see Warnings
and Precautions (5.3)]
Cardiovascular Thrombotic Events [see Warnings and Precautions (5.4)]
GI Bleeding, Ulceration and Perforation [see Warnings
and Precautions (5.5)]
Hepatotoxicity [see Warnings
and Precautions (5.6)]
Hypertension [see Warnings
and Precautions (5.7)]
Heart Failure
and Edema [see Warnings
and Precautions (5.8)]
Renal Toxicity
and Hyperkalemia [see Warnings
and Precautions (5.9)]
Hematologic Toxicity
[see Warnings and Precautions (5.12)]
Photosensitivity [see Warnings
and Precautions (5.15)]
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 another drug and may not reflect the rates observed in practice.
Of
the 423 subjects evaluable for safety in adequate and well-controlled trials,
211 were treated with Solaraze drug product and 212 were treated with a vehicle
gel …
7
Drug Interactions
PLR
conversion, as below:
See
Table 2 for clinically significant
drug interactions with diclofenac.
Table 2:
Clinically Significant Drug Interactions with Diclofenac (Newly added table; please refer to label for complete information)
8
Use in Specific Populations
8.2 Lactation
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Risk Summary
Data from published literature cases with oral
preparations of diclofenac indicate the presence of small amounts of diclofenac
in human milk. There are no data on
the effects on the breastfed infant, or the effects on milk production. The
developmental and health benefits of breastfeeding should be considered along
with the mother’s clinical need for Solaraze and any potential adverse effects
on the breastfed infant from the Solaraze or from the underlying maternal
condition.
Data
One woman treated orally with a diclofenac salt, 150
mg/day, had a milk diclofenac level of 100 mcg/L, equivalent to an infant dose
of about 0.03 mg/kg/day. Diclofenac was not detectable in breast milk in 12
women using diclofenac (after either 100 mg/day orally for 7 days or a single
50 mg intramuscular dose administered in the immediate postpartum period). The
systemic bioavailability after topical application of Solaraze is lower than
after oral dosing [see Clinical
Pharmacology (12.3).
8.3 Females and
Males of Reproductive Potential
PLLR conversion created newly added subsection:
Female Infertility
Based on the mechanism of action, the use of
prostaglandin mediated NSAIDs, including Solaraze, may delay or prevent rupture
of ovarian follicles, which has been associated with reversible infertility in
some women [see Clinical Pharmacology
(12.1)].
Published animal studies have shown that administration of prostaglandin
synthesis inhibitors has the potential to disrupt prostaglandin-mediated
follicular rupture required for ovulation. Small studies in women treated with
NSAIDs have also shown a reversible delay in ovulation. Consider withdrawal of
NSAIDs, including Solaraze, in women who have difficulties conceiving or who
are undergoing investigation of infertility.
8.5 Geriatric Use
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Elderly patients, compared to younger patients, are
at greater risk for NSAID-associated serious cardiovascular, gastrointestinal,
and/or renal adverse reactions. If the anticipated benefit for the elderly
patient outweighs these potential risks, start dosing at the low end of the
dosing range, and monitor patients for adverse effects [see Warnings and Precautions (5.4, 5.5, 5.6, 5.9, 5.14)].
Of the 211 subjects treated with Solaraze in
controlled clinical trials, 143 subjects were 65 years of age and over …
8.1 Pregnancy
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Additions and/or revisions underlined:
Risk Summary
Use
of NSAIDs, including Solaraze, can cause premature closure of the fetal ductus
arteriosus and fetal renal dysfunction leading
to oligohydramnios and, in some cases, neonatal
renal impairment. Because
of these risks,
limit dose and duration
of Solaraze use between about 20 and 30 weeks of gestation and avoid Solaraze
use at about 30 weeks of gestation and later in pregnancy.
Oligohydramnios/Neonatal Renal Impairment
Use of NSAIDs
at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction
leading to oligohydramnios, and in some cases, neonatal renal impairment.
Premature Closure
of Fetal Ductus Arteriosus
Use of NSAIDs, including
Solaraze, at about 30 weeks gestation or later in pregnancy increases
the risk of premature
closure of the fetal ductus arteriosus …
…
In published animal studies, prostaglandin synthesis inhibitors have been
reported to impair kidney development when administered at clinically relevant
doses.
The
background risk of major birth defects and miscarriage for the indicated
population(s) 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.
Clinical Considerations
Fetal/Neonatal Adverse Reactions
Premature Closure of Fetal Ductus Arteriosus
Avoid use of NSAIDs in women at about 30 weeks
gestation and later in pregnancy, because NSAIDs, including Solaraze, can
cause premature closure of the fetal ductus arteriosus.
Oligohydramnios/Neonatal Renal Impairment
If after careful consideration of alternative
treatment options for actinic keratoses, an NSAID
is necessary at about 20 weeks gestation or later in pregnancy, limit the use
to the lowest effective dose and shortest duration possible. If Solaraze
treatment extends beyond 48 hours, consider monitoring with ultrasound for
oligohydramnios. If oligohydramnios occurs, discontinue Solaraze and follow up
according to clinical practice.
Labor or Delivery
There are no studies on the effects of Solaraze
during labor or delivery. In animal studies, NSAIDS, including diclofenac,
inhibit prostaglandin synthesis, cause delayed parturition, and increase the
incidence of stillbirth.
Data
Human Data
Premature Closure of Fetal Ductus Arteriosus
Published literature reports that the use of NSAIDs
at about 30 weeks of gestation and later in pregnancy may cause premature
closure of the fetal ductus arteriosus …
… Because the published safety data on neonatal
outcomes involved mostly preterm infants, the generalizability of certain
reported risks to the full-term infant exposed to NSAIDs through maternal use
is uncertain.
Animal Data
The multiples provided in this labeling are based on
an MRHD that assumes 10% bioavailability following topical application of 2 g
Solaraze per day (1 mg/kg diclofenac sodium).
Reproductive studies performed with diclofenac
sodium alone at oral doses up to 20 mg/kg/day (15 times the MRHD based on body
surface area (BSA) comparisons) in mice, 10 mg/kg/day (15 times the MRHD based
on BSA comparisons) in rats, and 10 mg/kg/day (30 times the MRHD based on BSA
comparisons) in rabbits have revealed no evidence of malformations despite the
induction of maternal toxicity. In rats,
maternally toxic doses were associated with dystocia, prolonged gestation,
reduced fetal weights and growth, and reduced fetal survival. Diclofenac has
been shown to cross the placental barrier in mice and rats.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
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Do
not use Solaraze:
if you have had an allergic reaction to any of the ingredients in
Solaraze. See the end of this Medication Guide for a complete list of
ingredients in Solaraze.
if you have a history of asthma, hives, or other allergic-type reactions
after taking aspirin or other NSAIDs. Severe allergic reactions that can
sometimes lead to death, have happened in people with a history of these types
of allergic reactions to NSAIDs.
on skin that is inflamed, or has eczema, infected sores (lesions), burns
or wounds.
right before or after heart bypass surgery.
How
should I use Solaraze?
Apply enough Solaraze to cover each skin lesion (usually
a pea-sized amount) and gently rub in.
Avoid getting Solaraze in your eyes, nose and mouth.
If Solaraze gets into your eyes, nose or mouth wash out your eyes, nose or
mouth with water or saline right away. Call your healthcare provider if
irritation continues for more than 1 hour.
What should
I avoid while using Solaraze?
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Avoid
spending time in sunlight or artificial light, such as tanning beds or
sunlamps. Solaraze can make your skin sensitive to sunlight and the light from
tanning beds and sunlamps. Talk to your healthcare provider about sun
protection measures and wear loose-fitting clothes that cover your skin while out in sunlight. Stop using Solaraze
if you notice that you are beginning to get sunburn.
Do not apply Solaraze to open skin wounds, skin infections, or peeling skin.
What are the possible
side effects of Solaraze?
Solaraze and other NSAIDs can cause serious side effects, including:
See “What is the most important
information I should
know about Solaraze
and medicines called
Nonsteroidal Anti-inflammatory Drugs (NSAIDs)?
worsening of asthma in people who are aspirin-sensitive
If you take too much NSAID, call your healthcare provider
or get medical help right away.
Solaraze may cause fertility
problems in females,
which may affect
your ability to have a child. Talk to your healthcare
provider if this a concern for you.
These are not all of the possible side effects of NSAIDs. For more information, ask your healthcare provider or
pharmacist about NSAIDs.
PATIENT COUNSELING INFORMATION
PLR conversion; newly created section. Please refer to label for complete
information.
Other
PLR and PLLR conversions.
Approved Drug Label (PDF)
5
Warnings and Precautions
WARNINGS
Additions underlined
Fetal Toxicity
Premature Closure of Fetal Ductus Arteriosus:
Avoid use of NSAIDs, including Solaraze® Gel, in
pregnant women at about 30 weeks gestation and later. NSAIDs including
Solaraze® Gel, increase the risk of premature closure of the fetal ductus
arteriosus at approximately this gestational age.
Oligohydramnios/Neonatal Renal Impairment:
Use of NSAIDs, including Solaraze® Gel, at about 20
weeks gestation or later in pregnancy may cause fetal renal dysfunction leading
to oligohydramnios and, in some cases, neonatal renal impairment. These adverse
outcomes are seen, on average, after days to weeks of treatment, although
oligohydramnios has been infrequently reported as soon as 48 hours after NSAID
initiation. Oligohydramnios is often, but not always, reversible with treatment
discontinuation. Complications of prolonged oligohydramnios may, for example,
include limb contractures and delayed lung maturation. In some postmarketing
cases of impaired neonatal renal function, invasive procedures such as exchange
transfusion or dialysis were required.
If NSAID treatment is necessary between about 20
weeks and 30 weeks gestation, limit Solaraze® Gel use to the lowest effective
dose and shortest duration possible. Consider ultrasound monitoring of amniotic
fluid if Solaraze® Gel treatment extends beyond 48 hours. Discontinue Solaraze®
Gel if oligohydramnios occurs and follow up according to clinical practice [see
PRECAUTIONS; Pregnancy].
…
Serious
Skin Reactions, Drug Rash with Eosinophilia and Systemic Symptoms (DRESS).
Drug Rash with Eosinophilia and Systemic Symptoms (DRESS)
Drug Reaction with
Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking
NSAIDs such as Solaraze® Gel. Some of these events have been fatal or
life-threatening. DRESS typically, although not exclusively, presents with
fever, rash, lymphadenopathy, and/or facial swelling. Other clinical
manifestations may include hepatitis, nephritis, hematological abnormalities,
myocarditis, or myositis. Sometimes symptoms of DRESS may resemble an acute
viral infection. Eosinophilia is often present. Because this disorder is
variable in its presentation, other organ systems not noted here may be
involved. It is important to note that early manifestations of
hypersensitivity, such as fever or lymphadenopathy, may be present even though
rash is not evident. If such signs or symptoms are present, discontinue
Solaraze® Gel and evaluate the patient immediately.
…
8
Use in Specific Populations
Pregnancy:
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING
INFORMATION
Information for
Patients
Additions underlined
Fetal Toxicity
If treatment with Solaraze® Gel is needed for a pregnant woman between
about 20 to 30 weeks gestation, advise her that she may need to be monitored
for oligohydramnios, if treatment continues for longer than 48 hours. Inform
pregnant women to avoid use of Solaraze® Geland other NSAIDs starting at 30
weeks gestation because of the risk of the premature closing of the fetal
ductus arteriosus. [see WARNINGS; Fetal Toxicity, PRECAUTIONS; Pregnancy].
…
Serious Skin Reactions, including DRESS
Advise patients to stop taking Solaraze® Gel immediately
if they develop any type of rash or fever and to contact their healthcare
provider as soon as possible [see WARNINGS, Serious Skin Reactions ].
…
MEDICATION GUIDE
Additions underlined
…
Before
using Solaraze Gel, tell your healthcare provider about all of your medical
conditions, including if you:
have liver or kidney problems
have high blood pressure
have asthma
are pregnant or plan to become pregnant. Taking NSAIDS at about 20
weeks of pregnancy or later may harm your unborn baby. If you need to take
NSAIDs for more than 2 days when you are between 20 and 30 weeks of pregnancy,
your healthcare provider may need to monitor the amount of fluid in your womb
around your baby. You should not take NSAIDs after about 30 weeks of
pregnancy.
are breastfeeding or plan to breastfeed. You and your healthcare provider
should decide if you will use Solaraze Gel or breastfeed. You should not do
both.
…
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