Approved Drug Label (PDF)
5
Warnings and Precautions
5.9 Serious Skin Reactions
Additions and/or revisions underlined:
NSAIDs,
including diclofenac, can cause serious skin adverse reactions such as
exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal
necrolysis (TEN), which can be fatal. NSAIDs can also cause fixed drug
eruption (FDE). FDE may present as a more severe variant known as generalized
bullous fixed drug eruption (GBFDE), which can be life-threatening. These
serious events may occur without warning. Inform patients about the signs and
symptoms of serious skin reactions, and to discontinue the use of CAMBIA at the
first appearance of skin rash or any other sign of hypersensitivity.CAMBIA is
contraindicated in patients with previous serious skin reactions to NSAIDs [see Contraindications (4)].
6
Adverse Reactions
6.2 Postmarketing Experience
Additions
and/or revisions underlined:
…
Adverse Reactions
Reported With Diclofenac and Other NSAIDs
…
Other
less frequently occurring adverse reactions identified during post approval use
of diclofenac and other NSAIDs include fixed drug eruption [see Warnings and Precautions (5.9)].
…
Approved Drug Label (PDF)
8
Use in Specific Populations
8.1 Pregnancy
(PLLR conversion;
please refer to label)
8.2 Lactation
(PLLR conversion)
Risk
Summary
Data
from published literature reports 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 CAMBIA and any potential adverse effects on the breastfed infant from CAMBIA
or from the underlying maternal condition.
8.3 Females and Males of Reproductive Potential
(PLLR conversion)
Infertility
Females
Based
on the mechanism of action, the use of prostaglandin-mediated NSAIDs, including
CAMBIA, may delay or prevent rupture of ovarian follicles, which has been
associated with reversible infertility in some women. 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 CAMBIA,
in women who have difficulties conceiving or who are undergoing investigation
of infertility.
Approved Drug Label (PDF)
5
Warnings and Precautions
5.10 Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
(Newly added
subsection)
Drug Reaction with Eosinophilia and Systemic
Symptoms (DRESS) has been reported in patients taking NSAIDs such as CAMBIA.
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 CAMBIA and evaluate the patient immediately.
5.12 Fetal Toxicity
(Subsection title revised; Additions and/or revisions underlined)
Premature Closure of Fetal Ductus Arteriosus
Avoid use of NSAIDs, including CAMBIA, in pregnant women at about 30 weeks
gestation and later. NSAIDs, including CAMBIA, increase the risk of premature
closure of the fetal ductus arteriosus at approximately this gestational
age.
Oligohydramnios/Neonatal Renal Impairment
Use of NSAIDs, including CAMBIA, 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 CAMBIA use to the lowest
effective dose and shortest duration possible. Consider ultrasound monitoring
of amniotic fluid if CAMBIA treatment extends beyond 48 hours. Discontinue
CAMBIA if oligohydramnios occurs and follow up according to clinical practice
[see Use in Specific Population (8.1)].
6
Adverse Reactions
(Addition of the
following to the bulleted line listing)
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
(Extensive changes
to table; please refer to label)
PATIENT COUNSELING INFORMATION
(Additions and/or
revisions underlined)
…
Serious
Skin Reactions, Including DRESS
Advise
patients to stop taking CAMBIA immediately if they develop any type of
rash, blisters, fever or other signs of hypersensitivity such as itching and to
contact their healthcare provider as soon as possible. CAMBIA, like other
NSAIDs, can cause serious skin reactions such as exfoliative dermatitis,
Steven-Johnson
syndrome (SJS), toxic epidermal necrosis (TEN), and DRESS, which may result in
hospitalizations and even death [see
Warnings and Precautions (5.9, 5.10)].
Medication
Overuse Headache
Inform
patients that use of acute migraine drugs for 10 or more days per month may
lead to an exacerbation of headache and encourage patients to record headache frequency
and drug use (e.g., by keeping a headache diary) [see Warnings and Precautions (5.11)].
Fetal
Toxicity
Inform
pregnant women to avoid use of CAMBIA and other NSAIDs starting at 30
weeks gestation because of the risk of the premature closing of
the fetal ductus arteriosus. If treatment with CAMBIA 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 [see Warnings and
Precautions (5.12 and Use in Specific Populations (8.1)].
Lactation
Advise
patients to notify their healthcare provider if they are breastfeeding or plan to
breastfeed [see Use in specific
Populations (8.2)].
Female
Fertility
Advise
females of reproductive potential who desire pregnancy that NSAIDs, including
CAMBIA, may delay or prevent rupture of ovarian follicles, which has been associated
with reversible infertility in some women [see
Use in Specific Populations (8.3)].
Avoid
Concomitant Use of NSAIDs
Inform
patients that the concomitant use of CAMBIA with other NSAIDs or salicylates (e.g.,
diflunisal, salsalate) is not recommended due to the increased risk of
gastrointestinal toxicity, and little or no increase in efficacy [see Warnings and Precautions (5.2) and Drug Interactions (7)]. Alert patients that
NSAIDs may be present in “over the counter” medications for treatment of colds,
fever, or insomnia.
Use
of NSAIDS and Low-Dose Aspirin
Inform
patients not to use low-dose aspirin concomitantly with CAMBIA until they talk to
their healthcare provider [see Drug
Interactions (7)].
Approved Drug Label (PDF)
5
Warnings and Precautions
5.10 Medication Overuse Headache
(Newly added subsection)
Overuse of acute
migraine drugs (e.g., ergotamine, triptans, opioids, nonsteroidal
anti-inflammatory drugs or combination of these drugs for 10 or more days per
month) may lead to exacerbation of headache (medication overuse headache).
Medication overuse headache may present as migraine-like daily headaches or as
a marked increase in frequency of migraine attacks. Detoxification of patients,
including withdrawal of the overused drugs and treatment of withdrawal symptoms
(which often includes a transient worsening of headache) may be necessary.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION
(Additions and/or revisions are underlined)
Medication
Overuse Headache
Inform patients
that use of acute migraine drugs for 10 or more days per month may lead to an
exacerbation of headache and encourage patients to record headache frequency and
drug use (e.g., by keeping a headache diary).
Medication Guide
(Additions and/or revisions are underlined)
What are the
possible side effects of CAMBIA? CAMBIA can cause serious side effects,
including:
See “What is the
most important information I should know about CAMBIA?"