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Ambator Diclofenac Patch

Generic Name: diclofenac sodium
Dosage Form: patch

Medically reviewed by Drugs.com. Last updated on Nov 21, 2019.

Disclaimer: This drug has not been found by FDA to be safe and effective, and this labeling has not been approved by FDA. For further information about unapproved drugs, click here.

Active Ingredient:

Diclofenac Sodium   1.5%

Topical Anesthetic

Indications:  For the temporary relief of minor pain, swelling, inflammation and stiffness caused by

arthritis, simpe backache, sprains, bruises and strains.

Warnings:

  • For external use only.
  • Avoid contact with eyes.
  • Do not apply to wounds or damaged skin.
  • Do not use with bandage, wrap, brace, stocking or similar device or garment.
  • Do not use in combination with any other external analgesic products. 
  • If symptoms persist for more than seven days, discontinue use and consult a physician.
  • Keep out of reach of children. If swallowed, consult physician.
  • Do not bandage tightly.
  • If pregnant of breast feeding, contact physician prior to use.

Directions:

  • Clean and dry affected area.
  • Remove patch from backing and apply to affected area.
  • Use only one patch at a time, and not more than four patches r day.
  • Children under 12 should consult physician prior to use.

Additional information:  Store at room temperature. avoid direct sunlight.

Other ingredients:

Aqua (Purified Water), Dihydroxyaluminum Aminoacetate, Glycerol, Kaolin, Methyl Paraben, Polyacrylic Acid, olysorbate-80,

Propyl Paraben, Propylene Glycol, PVP, Sodium Polyacrylate, Tartaric Acid, Titanium Dioxide.

AMBATOR DICLOFENAC 1.5% PATCH - diclofenac sodium patch 7T PHARMA
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use Ambator Diclofenac Patch® safely
and effectively. See full prescribing information for Ambator Diclofenac Patch.

Ambator Diclofenac Patch® (diclofenac sodium patch) 1.5%, for topical use

WARNING: RISK OF SERIOUS CARDIOVASCULAR 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 (5.1)
Ambator Diclofenac Patch is contraindicated in the setting of coronary artery bypass graft
(CABG) surgery (4, 5.1)
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 (5.2)

INDICATIONS AND USAGE
• Ambator Diclofenac Patch contains diclofenac sodium, a nonsteroidal anti-inflammatory drug
(NSAID), and is indicated for the topical treatment of temporary relief of minor pain, swelling,
inflammation and stiffness caused by arthritis, simple backache, sprains, bruises and strains. (1)

DOSAGE AND ADMINISTRATION
• Use the lowest effective dosage for shortest duration consist with the individual patient
treatment goals (2.1)
• The recommended dose of Ambator Diclofenac Patch is one (1) patch to the most painful area
twice a day. (2)
• Ambator Diclofenac Patch should not be applied to damaged or non-intact skin. (2)

DOSAGE FORMS AND STRENGTHS
Ambator Diclofenac Patch® (diclofenac sodium patch) 1.5%, for topical use. Each individual patch is
embossed. (3)

CONTRAINDICATIONS
• Known hypersensitivity to diclofenac or any components of the drug product (4)
• History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other
NSAIDs (4)
• In the setting of CABG surgery (4)
• For use on non-intact or damaged skin (4)

WARNINGS AND PRECAUTIONS
• Hepatotoxicity: Inform patients of warning signs and symptoms of hepatotoxicity. Discontinue if
abnormal liver tests persist or worsen or if clinical signs and symptoms of liver disease develop
(5.3)
• Hypertension: Patients taking some antihypertensive medications may have impaired response to
these therapies when taking NSAIDs. Monitor blood pressure (5.4, 7)
• Heart Failure and Edema: Avoid use of Ambator Diclofenac Patch in patients with severe heart
failure unless benefits are expected to outweigh risk of worsening heart failure (5.5)
• Renal Toxicity: Monitor renal function in patients with renal or hepatic impairment, heart
failure, dehydration, or hypovolemia. Avoid use of Ambator Diclofenac Patch in patients with
advanced renal disease unless benefits are expected to outweigh risk of worsening renal function
(5.6)• Anaphylactic Reactions: Seek emergency help if an anaphylactic reaction occurs (5.7)
• Exacerbation of Asthma Related to Aspirin Sensitivity: Ambator Diclofenac Patch is
contraindicated in patients with aspirin-sensitive asthma. Monitor patients with preexisting asthma
(without aspirin sensitivity) (5.8)
• Serious Skin Reactions: Discontinue Ambator Diclofenac Patch at first appearance of skin rash
or other signs of hypersensitivity (5.9)
• Premature Closure of Fetal Ductus Arteriosus: Avoid use in pregnant women starting at 30
weeks gestation (5.10, 8.1)
• Hematologic Toxicity: Monitor hemoglobin or hematocrit in patients with any signs or symptoms
of anemia (5.11, 7)

ADVERSE REACTIONS
Most common adverse reactions are application site conditions, occurring in 11% and 12%,
respectively, of Ambator Diclofenac Patch and Placebo Patch-treated patients (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact 7T Pharma at 1-800-941-2848 or FDA at 1-800-FDA-1088
or www.fda.gov/medwatch.

DRUG INTERACTIONS
• Drugs that Interfere with Hemostasis (e.g. warfarin, aspirin, SSRIs/SNRIs): Monitor patients for
bleeding who are concomitantly using Ambator Diclofenac Patchwith drugs that interfere with
hemostasis. Concomitant use of Ambator Diclofenac Patch and analgesic doses of aspirin is not
generally recommended (7)
• ACE Inhibitors, Angiotensin Receptor Blockers (ARB), or Beta-Blockers: Concomitant use with
Ambator Diclofenac Patch may diminish the antihypertensive effect of these drugs. Monitor blood
pressure (7)
• ACE Inhibitors and ARBs: Concomitant use with Ambator Diclofenac Patchin elderly, volume
depleted, or those with renal impairment may result in deterioration of renal function. In such
high risk patients, monitor for signs of worsening renal function (7)

• Diuretics: NSAIDs can reduce natriuretic effect of furosemide and thiazide diuretics. Monitor
patients to assure diuretic efficacy including antihypertensive effects (7)
• Digoxin: Concomitant use with Ambator Diclofenac Patch may increase serum concentration and
prolong half-life of digoxin. Monitor serum digoxin levels (7)

USE IN SPECIFIC POPULATIONS
• Pregnancy: Use of NSAIDs during the third trimester of pregnancy increases the risk of premature
closure of the fetal ductus arteriosus. Avoid use of NSAIDs in pregnant women starting at 30 weeks
gestation (5.10, 8.1)
• Infertility: NSAIDs are associated with reversible infertility. Consider withdrawal of AMBATOR
DICLOFENAC PATCH in women who have difficulties conceiving (8.3)

See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.
Revised: 9/2017

FULL PRESCRIBING INFORMATION

WARNING: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS
Cardiovascular Thrombotic Events
• 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 [see Warnings and Precautions
(5.1)].
• Ambator Diclofenac Patch is contraindicated in the setting of coronary artery bypass graft
(CABG) surgery [see Contraindications
(4) and Warnings and Precautions (5.1)].

Gastrointestinal Bleeding, Ulceration, and Perforation
• 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
[see Warnings and Precautions (5.2)].

1 INDICATIONS AND USAGE
Ambator Diclofenac Patch® is indicated for the temporary relief of minor pain, swelling,
inflammation and stiffness caused by arthritis, simple backache, sprains, bruises and strains.

2 DOSAGE AND ADMINISTRATION

2.1 General Dosing Instructions
Use the lowest effective dosage for the shortest duration consistent with individual patient
treatment goals [see Warnings and Precautions (5)]. The recommended dose of AMBATOR DICLOFENAC
PATCH is one (1) patch to the most painful area twice a day.
2.2 Special Precautions
• Inform patients that, if Ambator Diclofenac Patch begins to peel-off, the edges of the patch
may be taped down. If problems with adhesion persist, patients may overlay the patch with a mesh
netting sleeve, where appropriate (e.g. to secure patches applied to ankles, knees, or elbows). The
mesh netting sleeve (e.g. Curad® Hold Tite™, Surgilast® Tubular Elastic Dressing) must allow air to
pass through and not be occlusive (non-breathable).
• Do not apply Ambator Diclofenac Patch to non-intact or damaged skin resulting from any etiology
e.g. exudative dermatitis, eczema, infected lesion, burns or wounds.
• Do not wear a Ambator Diclofenac Patch when bathing or showering.
• Wash your hands after applying, handling or removing the patch.
• Avoid eye contact
• Do not use combination therapy with Ambator Diclofenac Patch and an oral NSAID unless the benefit
outweighs the risk and conduct periodic laboratory evaluations.

3 DOSAGE FORMS AND STRENGTHS
Ambator Diclofenac Patch (diclofenac sodium 1.5%) Patch (12.5 × 8.5 cm) containing 180 mg of
diclofenac sodium, embossed with Ambator Diclofenac Patch 1.5%<DICLOFENAC SODIUM TOPICAL
PATCH>1.5%.

4 CONTRAINDICATIONS
Ambator Diclofenac Patch is contraindicated in the following patients:
• Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to diclofenac or
any components of the drug product [see Warnings and Precautions (5.7, 5.9)]
• 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 (5.7, 5.8)]
• In the setting of coronary artery bypass graft (CABG) surgery [see Warnings and Precautions
(5.1)]
• Ambator Diclofenac Patch is contraindicated for use on non-intact or damaged skin resulting from
any etiology, including exudative dermatitis, eczema, infection lesions, burns or wounds.

5 WARNINGS AND PRECAUTIONS

5.1 Cardiovascular Thrombotic Events
Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration
have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial
infarction (MI) and stroke, which can be fatal. Based on available data, it is unclear that the
risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV
thrombotic events over baseline conferred by NSAID use appears to be similar in those with and
without known CV disease or risk factors for CV disease. However, patients with known CV disease or
risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their
increased baseline rate. Some observational studies found that this increased risk of serious CV
thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic
risk has been observed most consistently at higher doses.
To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest
effective dose for the shortest duration possible. Physicians and patients should remain alert for
the development of such events, throughout the entire treatment course, even in the absence of
previous CV symptoms. Patients should be informed about the symptoms of serious CV events and the
steps to take if they occur.
There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of
serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID,
such as diclofenac, increases the risk of serious gastrointestinal (GI) events [see Warnings and
Precautions (5.2)].
Status Post Coronary Artery Bypass Graft (CABG) Surgery
Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the
first 10–14 days following CABG surgery found an increased incidence of myocardial infarction and
stroke. NSAIDs are contraindicated in the setting of CABG [see Contraindications (4)].
Post-MI Patients
Observational studies conducted in the Danish National Registry have demonstrated that patients
treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death,
and all-cause mortality beginning in the first week of treatment. In this same cohort, the
incidence of death in the first year post-MI was 20 per 100 person years in NSAID-treated patients
compared to 12 per 100 person years in non-NSAID exposed patients. Although the absolute rate of
death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID
users persisted over at least the next four years of follow-up.
Avoid the use of Ambator Diclofenac Patch in patients with a recent MI unless the benefits are
expected to outweigh the risk of recurrent CV thrombotic events. If Ambator Diclofenac Patch is
used in patients with a recent MI, monitor patients for signs of cardiac ischemia.

5.2 Gastrointestinal Bleeding, Ulceration, and Perforation
NSAIDs, including diclofenac, cause serious gastrointestinal (GI) adverse events including
inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small intestine, or
large intestine, which can be fatal. These serious adverse events can occur at any time, with or
without warning symptoms, in patients treated with NSAIDs.
Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is
symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occurred in
approximately 1% of patients treated for 3-6 months, and in about 2%-4% of patients treated for one
year. However, even short-term NSAID therapy is not without risk.
Risk Factors for GI Bleeding, Ulceration, and Perforation
Patients with a prior history of peptic ulcer disease and/or GI bleeding who used NSAIDs had a
greater than 10-fold increased risk for developing a GI bleed compared to patients without these
risk factors. Other factors that increase the risk of GI bleeding in patients treated with NSAIDs
include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin,
anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older
age; and poor general health status. Most postmarketing reports of fatal GI events occurred in
elderly or debilitated patients. Additionally, patients with advanced liver disease and/or
coagulopathy are at increased risk for GI bleeding.
Strategies to Minimize the GI Risks in NSAID-treated patients:
• Use the lowest effective dosage for the shortest possible duration.
• Avoid administration of more than one NSAID at a time.

• Avoid use in patients at higher risk unless benefits are expected to outweigh the increased risk
of bleeding. For such patients, as well as those with active GI bleeding, consider alternate
therapies other than NSAIDs.
• Remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy.
• If a serious GI adverse event is suspected, promptly initiate evaluation and treatment, and
discontinue Ambator Diclofenac Patch PATCH until a serious GI adverse event is ruled out.
• In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, monitor patients
more closely for evidence of GI bleeding [see Drug Interactions (7)].

5.3 Hepatotoxicity
In clinical trials of oral diclofenac containing products, meaningful elevations (i.e., more than 3
times the ULN) of AST (SGOT) were observed in about 2% of approximately 5,700 patients at some time
during diclofenac treatment (ALT was not measured in all studies).
In a large open-label, controlled trial of 3,700 patients treated with oral diclofenac sodium for
2-6 months, patients were monitored first at 8 weeks and 1,200 patients were monitored again at 24
weeks. Meaningful elevations of ALT and/or AST occurred in about 4% of the 3,700 patients and
included marked elevations (greater than 8 times the ULN) in about 1% of the 3,700 patients. In
that open-label study, a higher incidence of borderline (less than 3 times the ULN), moderate (3-8
times the ULN), and marked (greater than 8 times the ULN) elevations of ALT or AST was observed in
patients receiving diclofenac when compared to other NSAIDs. Elevations in transaminases were seen
more frequently in patients with osteoarthritis than in those with rheumatoid arthritis.
Almost all meaningful elevations in transaminases were detected before patients became symptomatic.
Abnormal tests occurred during the first 2 months of therapy with diclofenac in 42 of the 51
patients in all trials who developed marked transaminase elevations.
In postmarketing reports, cases of drug-induced hepatotoxicity have been reported in the first
month, and in some cases, the first 2 months of therapy, but can occur at any time during treatment
with diclofenac. Postmarketing surveillance has reported cases of severe hepatic reactions,
including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver
failure. Some of these reported cases resulted in fatalities or liver transplantation.
In a European retrospective population-based, case-controlled study, 10 cases of diclofenac
associated drug-induced liver injury with current use compared with non-use of diclofenac were
associated with a statistically significant 4-fold adjusted odds ratio of liver injury. In this
particular study, based on an overall number of 10 cases of liver injury associated with
diclofenac, the adjusted odds ratio increased further with female gender, doses of 150 mg or more,
and duration of use for more than 90 days.
Physicians should measure transaminases at baseline and periodically in patients receiving
long-term therapy with diclofenac, because severe hepatotoxicity may develop without a prodrome of
distinguishing symptoms. The optimum times for making the first and subsequent transaminase
measurements are not known. Based on clinical trial data and postmarketing experiences,
transaminases should be monitored within 4 to 8 weeks after initiating treatment with diclofenac.
However, severe hepatic reactions can occur at any time during treatment with diclofenac.
If abnormal liver tests persist or worsen, if clinical signs and/or symptoms consistent with liver
disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, abdominal pain,
diarrhea, dark urine, etc.), Ambator Diclofenac Patch should be discontinued immediately.
Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue,
lethargy, diarrhea, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms).
If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations
occur (e.g., eosinophilia, rash, etc.), discontinue Ambator Diclofenac Patch immediately, and
perform a clinical evaluation of the patient.
To minimize the potential risk for an adverse liver related event in patients treated with AMBATOR
DICLOFENAC PATCH, use the lowest effective dose for the shortest duration possible. Exercise
caution when prescribing Ambator Diclofenac Patch with concomitant drugs that are known to be
potentially hepatotoxic (e.g., acetaminophen, antibiotics, anti-epileptics).

5.4 Hypertension
NSAIDs, including Ambator Diclofenac Patch, can lead to new onset of hypertension or worsening of
preexisting hypertension, either of which may contribute to the increased incidence of CV events.
Patients taking angiotensin converting enzyme (ACE) inhibitors, thiazide diuretics, or loop
diuretics may have impaired response to these therapies when taking NSAIDs [see Drug Interactions
(7)].
Monitor blood pressure (BP) during the initiation of NSAID treatment and throughout the course of
therapy.

5.5 Heart Failure and Edema
The Coxib and traditional NSAID Trialists' Collaboration meta-analysis of randomized controlled
trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in
COX-2 selective-treated patients and nonselective NSAID-treated patients compared to placebo-
treated patients. In a Danish National Registry study of patients with heart failure, NSAID use
increased the risk of MI, hospitalization for heart failure, and death.
Additionally, fluid retention and edema have been observed in some patients treated with NSAIDs.
Use of diclofenac may blunt the CV effects of several therapeutic agents used to treat these
medical conditions (e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers [ARBs]) [see
Drug Interactions (7)].
Avoid the use of Ambator Diclofenac Patch in patients with severe heart failure unless the benefits
are expected to outweigh the risk of worsening heart failure. If Ambator Diclofenac Patch is used
in patients with severe heart failure, monitor patients for signs of worsening heart failure.

5.6 Renal Toxicity and Hyperkalemia
Renal Toxicity
Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury.
Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role
in the maintenance of renal perfusion. In these patients, administration of an NSAID may cause a
dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which
may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those
with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those
taking diuretics and ACE inhibitors or ARBs, and the elderly. Discontinuation of NSAID therapy is
usually followed by recovery to the pretreatment state.
No information is available from controlled clinical studies regarding the use of AMBATOR
DICLOFENAC PATCH in patients with advanced renal disease. The renal effects of AMBATOR DICLOFENAC
PATCH may hasten the progression of renal dysfunction in patients with pre-existing renal disease.
Correct volume status in dehydrated or hypovolemic patients prior to initiating AMBATOR DICLOFENAC
PATCH. Monitor renal function in patients with renal or hepatic impairment, heart failure,
dehydration, or hypovolemia during use of Ambator Diclofenac Patch [see Drug Interactions (7)].
Avoid the use of Ambator Diclofenac Patch in patients with advanced renal disease unless the
benefits are expected to outweigh the risk of worsening renal function. If Ambator Diclofenac Patch
is used in patients with advanced renal disease, monitor patients for signs of worsening renal
function.
Hyperkalemia
Increases in serum potassium concentration, including hyperkalemia, have been reported with use of
NSAIDs, even in some patients without renal impairment. In patients with normal renal function,
these effects have been attributed to a hyporeninemic-hypoaldosteronism state.

5.7 Anaphylactic Reactions
Diclofenac has been associated with anaphylactic reactions in patients with and without known
hypersensitivity to diclofenac and in patients with aspirin-sensitive asthma [see Contraindications
(4) and Warnings and Precautions (5.8)].
Seek emergency help if an anaphylactic reaction occurs.

5.8 Exacerbation of Asthma Related to Aspirin Sensitivity
A subpopulation of patients with asthma may have aspirin-sensitive asthma which may include chronic
rhinosinusitis complicated by nasal polyps; severe, potentially fatal bronchospasm; and/or
intolerance to aspirin and other NSAIDs. Because cross-reactivity between aspirin and other NSAIDs
has been reported in such aspirin-sensitive patients, Ambator Diclofenac Patch is contraindicated
in patients with this form of aspirin sensitivity [see Contraindications (4)]. When AMBATOR
DICLOFENAC PATCH is used in patients with preexisting asthma (without known aspirin sensitivity),
monitor patients for changes in the signs and symptoms of asthma.

5.9 Serious Skin Reactions
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. These serious events may occur without warning. Inform patients about the signs and symptoms
of serious skin reactions, and to discontinue the use of Ambator Diclofenac Patch at the first
appearance of skin rash or any other sign of hypersensitivity. Ambator Diclofenac Patch is
contraindicated in patients with previous serious skin reactions to NSAIDs
[see Contraindications (4)].

5.10 Premature Closure of Fetal Ductus Arteriosus
Diclofenac may cause premature closure of the fetal ductus arteriosus. Avoid use of NSAIDs,
including Ambator Diclofenac Patch, in pregnant women starting at 30 weeks of gestation (third
trimester) [see Use in Specific Populations (8.1)].

5.11 Hematologic Toxicity
Anemia has occurred in NSAID-treated patients. This may be due to occult or gross blood loss, fluid
retention, or an incompletely described effect on erythropoiesis. If a patient treated with AMBATOR
DICLOFENAC PATCH has any signs or symptoms of anemia, monitor hemoglobin or hematocrit.
NSAIDs, including Ambator Diclofenac Patch, may increase the risk of bleeding events. Co-morbid
conditions such as coagulation disorders, concomitant use of warfarin, other anticoagulants,
antiplatelet agents (e.g., aspirin), serotonin reuptake inhibitors (SSRIs) and serotonin
norepinephrine reuptake inhibitors (SNRIs) may increase this risk. Monitor these patients for signs
of bleeding [see Drug Interactions (7)].

5.12 Masking of Inflammation and Fever
The pharmacological activity of Ambator Diclofenac Patch in reducing inflammation, and possibly
fever, may diminish the utility of diagnostic signs in detecting infections.

5.13 Laboratory Monitoring
Because serious GI bleeding, hepatotoxicity, and renal injury can occur without warning symptoms or
signs, consider monitoring patients on long- term NSAID treatment with a CBC and a chemistry
profile periodically [see Warnings and Precautions (5.2, 5.3, 5.6)].

5.14 Accidental Exposure in Children
Even a used Ambator Diclofenac Patch contains a large amount of diclofenac sodium (as much as 170
mg). The potential therefore exists for a small child or pet to suffer serious adverse effects from
chewing or ingesting a new or used Ambator Diclofenac Patch. It is important for patients to store
and dispose of Ambator Diclofenac Patch out of the reach of children and pets.

5.15 Eye Exposure
Avoid contact of Ambator Diclofenac Patch with eyes and mucosa. Advise patients that if eye contact
occurs, immediately wash out the eye with water or saline and consult a physician if irritation
persists for more than an hour.

5.16 Oral Nonsteroidal Anti-inflammatory Drugs
Concomitant use of oral and topical NSAIDs may result in a higher rate of hemorrhage, more frequent
abnormal creatinine, urea and hemoglobin. Do not use combination therapy with Ambator Diclofenac
Patch and an oral NSAID unless the benefit outweighs the risk.

6 ADVERSE REACTIONS
The following adverse reactions are discussed in greater detail in other sections of the labeling:
• Cardiovascular Thrombotic Events [see Warnings and Precautions (5.1)]
• GI Bleeding, Ulceration and Perforation [see Warnings and Precautions (5.2)]
• Hepatotoxicity [see Warnings and Precautions (5.3)]
• Hypertension [see Warnings and Precautions (5.4)]
• Heart Failure and Edema [see Warnings and Precautions (5.5)]
• Renal Toxicity and Hyperkalemia [see Warnings and Precautions (5.6)]
• Anaphylactic Reactions [see Warnings and Precautions (5.7)]
• Serious Skin Reactions [see Warnings and Precautions (5.9)]
• Hematologic Toxicity [see Warnings and Precautions (5.11)]

6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates
observed in the clinical trials of a drug cannot be directly compared with rates in the clinical
trials of another drug and may not reflect the rates observed in practice.
In controlled trials during the premarketing development of Ambator Diclofenac Patch, approximately
600 patients with minor sprains, strains, and contusions were treated with Ambator Diclofenac Patch
for up to two weeks.
Adverse Events Leading to Discontinuation of Treatment
In the controlled trials, 3% of patients in both the Ambator Diclofenac Patch and placebo patch
groups discontinued treatment due to an adverse event. The most common adverse events leading to
discontinuation were application site reactions, occurring in 2% of both the AMBATOR DICLOFENAC
PATCH and placebo patch groups. Application site reactions leading to dropout included pruritus,
dermatitis, and burning.
Common Adverse Events
Localized Reactions
Overall, the most common adverse events associated with Ambator Diclofenac Patch treatment were
skin reactions at the site of treatment. Table 1 lists all adverse events, regardless of causality,
occurring in ≥ 1% of patients in controlled trials of Ambator Diclofenac Patch. A majority of
patients treated with Ambator Diclofenac Patch had adverse events with a maximum intensity of
"mild" or "moderate."
Table 1. Common Adverse Events (by body system and preferred term) in ≥ 1% of Patients treated with
Ambator Diclofenac Patch or Placebo Patch *

Category

Diclofenac N=572

Placebo N=564

N Percent N Percent

Table 1. Common Adverse Events (by body system and preferred term) in ≥ 1% of Patients treated with
Ambator Diclofenac Patch or Placebo Patch *

Category

Diclofenac N=572

Placebo N=564

N Percent N Percent
Application Site Conditions 64
11 70 12

Pruritus
31 5 44 8
Dermatitis
9 2 3 <1
Burning
2 <1 8 1
Other†
22 4 15 3
Gastrointestinal Disorders 49
9 33 6
Nausea
17 3 11 2
Dysgeusia
10 2 3 <1
Dyspepsia
7 1 8 1
Other‡
15 3 11 2
Nervous System Disorders 13
2 18 3
Headache
7 1 10 2
Paresthesia
6 1 8 1
Somnolence 4
1 6 1
Other §
4 1 3 <1

*The table lists adverse events occurring in placebo-treated patients because the placebo-patch was
comprised of the same ingredients as Ambator Diclofenac Patch except for diclofenac. Adverse events
in the placebo group may therefore reflect effects of the non-active ingredients.
† Includes: application site dryness, irritation, erythema, atrophy, discoloration, hyperhidriosis,
and vesicles.
‡ Includes: gastritis, vomiting, diarrhea, constipation, upper abdominal pain, and dry mouth.
§ Includes: hypoesthesia, dizziness, and hyperkinesias

Foreign labeling describes that dermal allergic reactions may occur with Ambator Diclofenac Patch
treatment. Additionally, the treated area may become irritated or develop itching, erythema, edema,
vesicles, or abnormal sensation.

7 DRUG INTERACTIONS
See Table 2 for clinically significant drug interactions with diclofenac.
Table 2: Clinically Significant Drug Interactions with Diclofenac

Drugs That Interfere with Hemostasis

Clinical Impact:

• Diclofenac and anticoagulants such as warfarin have a synergistic effect on bleeding. The
concomitant use of diclofenac and anticoagulants have an increased risk of serious bleeding
compared to the use of either drug alone.
• Serotonin release by platelets plays an important role in hemostasis. Case-control and cohort
epidemiological studies showed that concomitant use of drugs that interfere with serotonin reuptake
and an NSAID may potentiate the risk of

bleeding more than an NSAID alone.

Intervention:

Monitor patients with concomitant use of Ambator Diclofenac Patch with anticoagulants (e.g.,
warfarin), antiplatelet agents (e.g., aspirin), selective serotonin reuptake inhibitors (SSRIs),
and serotonin norepinephrine reuptake inhibitors (SNRIs) for signs of bleeding [see Warnings and
Precautions (5.11)].

Aspirin

Clinical Impact:

Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of
aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical
study, the concomitant use of an NSAID and aspirin was associated with a significantly increased
incidence of GI adverse reactions as compared to use of the NSAID alone
[see Warnings and Precautions (5.2)].

Intervention:

Concomitant use of Ambator Diclofenac Patch and analgesic doses of aspirin is not generally
recommended because of the increased risk of bleeding [see Warnings and Precautions (5.11)].

Ambator Diclofenac Patch is not a substitute for low dose aspirin for cardiovascular protection.
ACE Inhibitors, Angiotensin Receptor Blockers, and Beta-Blockers

Clinical Impact:

• NSAIDs may diminish the antihypertensive effect of angiotensin converting enzyme (ACE)
inhibitors, angiotensin receptor blockers (ARBs), or beta-blockers (including propranolol).
• In patients who are elderly, volume-depleted (including those on diuretic therapy), or have
renal impairment, co- administration of an NSAID with ACE inhibitors or ARBs may result in
deterioration of renal function, including possible acute renal failure. These effects are usually
reversible.

Intervention:

• During concomitant use of Ambator Diclofenac Patch and ACE-inhibitors, ARBs, or
beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained.
• During concomitant use of Ambator Diclofenac Patch and ACE-inhibitors or ARBs in patients who are
elderly, volume- depleted, or have impaired renal function, monitor for signs of worsening renal
function [see Warnings and Precautions (5.6)].
• When these drugs are administered concomitantly, patients should be adequately hydrated. Assess
renal function at the beginning of the concomitant treatment and periodically thereafter.

Diuretics

Clinical Impact:

Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the
natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients.
This effect has been attributed to the NSAID inhibition of renal prostaglandin synthesis.

Intervention:

During concomitant use of Ambator Diclofenac Patch with diuretics, observe patients for signs of
worsening renal function, in addition to assuring diuretic efficacy including antihypertensive
effects [see Warnings and Precautions (5.6)].

Digoxin

Clinical Impact:

The concomitant use of diclofenac with digoxin has been reported to increase the serum
concentration and prolong the half- life of digoxin.

Intervention: During concomitant use of Ambator Diclofenac Patch and digoxin, monitor
serum digoxin levels.

Lithium

Clinical Impact:

NSAIDs have produced elevations in plasma lithium levels and reductions in renal lithium clearance.
The mean minimum lithium concentration increased 15%, and the renal clearance decreased by
approximately 20%. This effect has been attributed to
NSAID inhibition of renal prostaglandin synthesis.

Intervention: During concomitant use of Ambator Diclofenac Patch and lithium, monitor
patients for signs of lithium toxicity.

Methotrexate

Clinical Impact:

Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (e.g.,
neutropenia, thrombocytopenia, renal dysfunction).

Intervention: During concomitant use of Ambator Diclofenac Patch and methotrexate,
monitor patients for methotrexate toxicity.

Cyclosporine

Clinical Impact: Concomitant use of Ambator Diclofenac Patch and cyclosporine may increase
cyclosporine's nephrotoxicity.

Intervention:

During concomitant use of Ambator Diclofenac Patch and cyclosporine, monitor patients for signs of
worsening renal function.

NSAIDs and Salicylates

Clinical Impact:

Concomitant use of diclofenac with other NSAIDs or salicylates (e.g., diflunisal, salsalate)
increases the risk of GI toxicity, with little or no increase in efficacy [see Warnings and
Precautions (5.2)].

Intervention: The concomitant use of diclofenac with other NSAIDs or salicylates is not
recommended.

Pemetrexed

Clinical Impact:

Concomitant use of Ambator Diclofenac Patch and pemetrexed may increase the risk of
pemetrexed-associated myelosuppression, renal, and GI toxicity (see the pemetrexed prescribing
information).

Intervention:

During concomitant use of Ambator Diclofenac Patch and pemetrexed, in patients with renal
impairment whose creatinine clearance ranges from 45 to 79 mL/min, monitor for myelosuppression,
renal and GI toxicity.
NSAIDs with short elimination half-lives (e.g., diclofenac, indomethacin) should be avoided for a
period of two days before, the day of, and two days following administration of pemetrexed.
In the absence of data regarding potential interaction between pemetrexed and NSAIDs with longer
half-lives (e.g., meloxicam, nabumetone), patients taking these NSAIDs should interrupt dosing for
at least five days before, the day of, and two days following pemetrexed administration.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy
Pregnancy Category C prior to 30 weeks gestation; Category D starting 30 weeks gestation. Risk
Summary
Use of NSAIDs, including Ambator Diclofenac Patch, during the third trimester of pregnancy
increases the risk of premature closure of the fetal ductus arteriosus. Avoid use of NSAIDs,
including Ambator Diclofenac Patch, in pregnant women starting at 30 weeks of gestation (third
trimester).
There are no adequate and well-controlled studies of Ambator Diclofenac Patch in pregnant women.
Data from observational studies regarding potential embryofetal risks of NSAID use in women in the
first or second trimesters of pregnancy are inconclusive. In the general U.S. population, all
clinically recognized pregnancies, regardless of drug exposure, have a background rate of 2-4% for
major malformations, and 15-20% for pregnancy loss.
In animal reproduction studies, diclofenac sodium administered orally to pregnant rats and rabbits
during the period of organogenesis produced embryotoxicity at approximately 3 and 7 times,
respectively, the topical exposure from the maximum recommended human dose (MRHD) of AMBATOR
DICLOFENAC PATCH. In rats, increased incidences of skeletal anomalies and maternal toxicity were
also observed at this dose. Diclofenac sodium administered orally to both male and female rats
prior to mating and throughout the mating period, and during gestation and lactation in females
produced embryotoxicity at doses approximately 3 and 7 times, respectively, the topical exposure
from the MRHD [see Data].
Based on animal data, prostaglandins have been shown to have an important role in endometrial
vascular permeability, blastocyst implantation, and decidualization. In animal studies,
administration of prostaglandin synthesis inhibitors such as diclofenac, resulted in increased pre-
and post- implantation loss.
Clinical Considerations

Labor or Delivery
There are no studies on the effects of Ambator Diclofenac Patch during labor or delivery. In animal
studies, NSAIDS, including diclofenac, inhibit prostaglandin synthesis, cause delayed parturition,
and increase the incidence of stillbirth.
Data
Animal data
Pregnant Sprague Dawley rats were administered 1, 3, or 6 mg/kg diclofenac sodium via oral gavage
daily from gestation days 6 to 15. Maternal toxicity, embryotoxicity, and increased incidence of
skeletal anomalies were noted with 6 mg/kg/day diclofenac sodium, which corresponds to 3 times the
maximum recommended daily exposure in humans based on a body surface area comparison. Pregnant New
Zealand White rabbits were administered 1, 3, or 6 mg/kg diclofenac sodium via oral gavage daily
from gestation days 6 to 18. No maternal toxicity was noted; however, embryotoxicity was evident at
6 mg/kg/day group which corresponds to 7 times the maximum recommended daily exposure in humans
based on a body surface area comparison.
Male rats were orally administered diclofenac sodium (1, 3, 6 mg/kg) for 60 days prior to mating
and throughout the mating period, and females were given the same doses 14 days prior to mating and
through mating, gestation, and lactation. Embryotoxicity was observed at 6 mg/kg diclofenac sodium
(3 times the maximum recommended daily exposure in humans based on a body surface area comparison),
and was manifested as an increase in early resorptions, post-implantation losses, and a decrease in
live fetuses. The number of live born and total born were also reduced as was F1 postnatal
survival, but the physical and behavioral development of surviving F1 pups in all groups was the
same as the deionized water control, nor was reproductive performance adversely affected despite a
slight treatment-related reduction in body weight.

8.2 Lactation
Risk Summary
Based on available data, diclofenac may be present in human milk. The developmental and health
benefits of breastfeeding should be considered along with the mother's clinical need for AMBATOR
DICLOFENAC PATCH and any potential adverse effects on the breastfed infant from the AMBATOR
DICLOFENAC PATCH 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 relative
bioavailability for Ambator Diclofenac Patch is <1% of a single 50 mg diclofenac tablet.

8.3 Females and Males of Reproductive Potential
Infertility
Females
Based on the mechanism of action, the use of prostaglandin-mediated NSAIDs, including AMBATOR
DICLOFENAC PATCH 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 Ambator Diclofenac Patch, in women who have difficulties
conceiving or who are undergoing investigation of infertility.

8.4 Pediatric Use
The safety and effectiveness of Ambator Diclofenac Patch in pediatric patients have not been
established.

8.5 Geriatric Use
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 (5.1, 5.2, 5.3, 5.6,
5.13)].
Clinical studies of Ambator Diclofenac Patch did not include sufficient numbers of subjects aged 65
and over to determine whether they respond differently from younger subjects. Other reported
clinical experience has not identified differences in responses between the elderly and younger
patients.

10 OVERDOSAGE
Symptoms following acute NSAID overdosages have been typically limited to lethargy, drowsiness,
nausea, vomiting, and epigastric pain, which have been generally reversible with supportive care.
Gastrointestinal bleeding has occurred. Hypertension, acute renal failure, respiratory depression,
and coma have occurred, but were rare [see Warnings and Precautions (5.1, 5.2, 5.4, 5.6)].

Manage patients with symptomatic and supportive care following an NSAID overdosage. There are no
specific antidotes. Forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may
not be useful due to high protein binding.
For additional information about overdosage treatment contact a poison control center
(1-800-222-1222).

11 DESCRIPTION
Ambator Diclofenac Patch (diclofenac sodiumPatch) is a nonsteroidal anti-inflammatory drug,
available for topical application. Ambator Diclofenac Patch is a 12.5 cm × 8.5 cm patch comprised
of an adhesive material containing 1.5% diclofenac sodium which is applied to a non-woven polyester
felt backing and covered with a polypropylene film release liner. The release liner is removed
prior to topical application to the skin.
The chemical name of diclofenac sodium is Sodium [o-(2,6-dichloranilino) phenyl] acetate, with a
molecular formula of C14H10Cl2NNaO2, and molecular weight 318.13, a benzene acetic acid derivate,
and the following chemical structure:

Each adhesive patch contains 180 mg of diclofenac sodium (13 mg per gram adhesive) in an aqueous
base. It also contains the following inactive ingredients: Aqua (Purified Water), Dihydroxyaluminum
Aminoacetate, Glycerol, Kaolin, Methyl Paraben, Polyacrylic Acid, Polysorbate-80, Propyl Paraben,
Propylene Glycol, PVP, Sodium Polyacrylate, Tartaric Acid, Titanium Dioxide

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action
Diclofenac has analgesic, anti-inflammatory, and antipyretic properties.
The mechanism of action of diclofenac, like that of other NSAIDs, is not completely understood but
involves inhibition of cyclooxygenase (COX-1 and COX-2).
Diclofenac is a potent inhibitor of prostaglandin synthesis in vitro. Diclofenac concentrations
reached during therapy have produced in vivo effects. Prostaglandins sensitize afferent nerves and
potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators
of inflammation. Because diclofenac is an inhibitor of prostaglandin synthesis, its mode of action
may be due to a decrease of prostaglandins in peripheral tissues.

12.2 Pharmacodynamics
Ambator Diclofenac Patch applied to intact skin provides local analgesia by releasing diclofenac
sodium from the patch into the skin.

12.3 Pharmacokinetics
Absorption
Following a single application of the Ambator Diclofenac Patch on the upper inner arm, peak plasma
concentrations of diclofenac (range
0.7 – 6 ng/mL) were noted between 10 – 20 hours of application. Plasma concentrations of diclofenac
in the range of 1.3 – 8.8 ng/mL were noted after five days with twice-a-day AMBATOR DICLOFENAC
PATCH application.
Systemic exposure (AUC) and maximum plasma concentrations of diclofenac, after repeated dosing for
four days with Ambator Diclofenac Patch, were lower (<1%) than after a single oral 50-mg diclofenac
sodium tablet.
The pharmacokinetics of Ambator Diclofenac Patch has been tested in healthy volunteers at rest or
undergoing moderate exercise (cycling 20 min/h for 12 h at a mean HR of 100.3 bpm). No clinically
relevant differences in systemic absorption were observed, with peak plasma concentrations in the
range of 2.2 – 8.1 ng/mL while resting, and 2.7 – 7.2 ng/mL during exercise.
Distribution

Diclofenac has a very high affinity (>99%) for human serum albumin. Diclofenac diffuses into and
out of the synovial fluid. Diffusion into the joint occurs when plasma levels are higher than those
in the synovial fluid, after which the process reverses and synovial fluid levels are higher than
plasma levels. It is not known whether diffusion into the joint plays a role in the effectiveness
of diclofenac.
Elimination
Metabolism
Five diclofenac metabolites have been identified in human plasma and urine. The metabolites include
4'-hydroxy-, 5-hydroxy-, 3'-hydroxy-, 4',5- dihydroxy- and 3'-hydroxy-4'-methoxy diclofenac. The
major diclofenac metabolite, 4'hydroxy-diclofenac, has very weak pharmacologic activity. The
formation of 4'-hydroxy diclofenac is primarily mediated by CPY2C9. Both diclofenac and its
oxidative metabolites undergo glucuronidation or sulfation followed by biliary excretion.
Acylglucuronidation mediated by UGT2B7 and oxidation mediated by CPY2C8 may also play a role in
diclofenac metabolism. CYP3A4 is responsible for the formation of minor metabolites, 5-hydroxy and
3'-hydroxy- diclofenac.
Excretion
The plasma elimination half-life of diclofenac after application of Ambator Diclofenac Patch is
approximately 12 hours. Diclofenac is eliminated through metabolism and subsequent urinary and
biliary excretion of the glucuronide and the sulfate conjugates of the metabolites. Little or no
free unchanged diclofenac is excreted in the urine. Approximately 65% of the dose is excreted in
the urine and approximately 35% in the bile as conjugates of unchanged diclofenac plus metabolites.
Specific Populations
The pharmacokinetics of Ambator Diclofenac Patch has not been investigated in children, patients
with hepatic or renal impairment, or specific racial groups.
Drug Interaction Studies
Aspirin: When NSAIDs were administered with aspirin, the protein binding of NSAIDs were reduced,
although the clearance of free NSAID was not altered. The clinical significance of this interaction
is not known. See Table 1 for clinically significant drug interactions of NSAIDs with aspirin
[see Drug Interactions (7)].

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis
Long-term studies in animals have not been performed to evaluate the carcinogenic potential of
either diclofenac sodium or Ambator Diclofenac Patch.
Mutagenesis
Diclofenac sodium is not mutagenic in Salmonella typhimurium strains, nor does it induce an
increase in metabolic aberrations in cultured human lymphocytes, or the frequency of micronucleated
cells in the bone marrow micronucleus test performed in rats.
Impairment of Fertility
The effect of diclofenac sodium on fertility in animals has been summarized in 8.1 under Animal
Data.
Male and female Sprague Dawley rats were administered 1, 3, or 6 mg/kg/day diclofenac sodium via
oral gavage (males treated for 60 days prior to conception and during mating period, females
treated for 14 days prior to mating through day 19 of gestation). Diclofenac sodium treatment with
6 mg/kg/day resulted in increased early resorptions and post-implantation losses; however, no
effects on the mating and fertility indices were found. The 6 mg/kg/day dose corresponds to 3 times
the maximum recommended daily exposure in humans based on a body surface area comparison.

14 CLINICAL STUDIES

14.1 Ankle Sprains
Efficacy of Ambator Diclofenac Patch was demonstrated in two of four studies of patients with minor
sprains, strains, and contusions. Patients were randomly assigned to treatment with the AMBATOR
DICLOFENAC PATCH, or a placebo patch identical to the Ambator Diclofenac Patch minus the active
ingredient. In the first of these two studies, patients with ankle sprains were treated once daily
for a week. In the second study, patients with sprains, strains and contusions were treated twice
daily for up to two weeks. Pain was assessed over the period of treatment. Patients treated with
the Ambator Diclofenac Patch experienced a greater reduction in pain as compared to patients
randomized to placebo patch as evidenced by the responder curves presented below (Figures 1-4).
Figure 1: Patients Achieving Various Levels of Pain Relief at Day 3; 14-Day Study

Figure 2: Patients Achieving Various Levels of Pain Relief at End of Study; 14-Day Study

Figure 3: Patients Achieving Various Levels of Pain Relief at Day 3; 7-Day Study

Figure 4: Patients Achieving Various Levels of Pain Relief at End of Study; 7-Day Study

16 HOW SUPPLIED/STORAGE AND HANDLING
The Ambator Diclofenac Patch is supplied in resealable envelopes, each containing 10 patches (12.5
cm × 8.5 cm), per box (NDC 70645- 0212-01). Each individual patch is embossed with "AMBATOR
DICLOFENAC PATCH<DICLOFENAC SODIUM TOPICAL PATCH>1.5%".
• Each patch contains 180 mg of diclofenac sodium in an aqueous base (13 mg of active per gram
of adhesive or 1.3%).
• The product is intended for topical use only.
• Keep out of reach of children and pets.
• Envelops should be sealed at all times when not in use.

Storage
Store at 20°C to 25°C (68°C to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see
USP Controlled Room Temperature].

17 PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Medication Guide) that accompanies
each prescription dispensed, as well as the Directions for Use on the product packaging. Inform
patients, families, or their caregivers of the following information before initiating therapy with
Ambator Diclofenac Patch and periodically during the course of ongoing therapy.
Cardiovascular Thrombotic Events
Advise patients to be alert for the symptoms of cardiovascular thrombotic events, including chest
pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to
their health care provider immediately [see Warnings and Precautions (5.1)].
Gastrointestinal Bleeding, Ulceration, and Perforation
Advise patients to report symptoms of ulcerations and bleeding, including epigastric pain,
dyspepsia, melena, and hematemesis to their health care provider. In the setting of concomitant use
of low-dose aspirin for cardiac prophylaxis, inform patients of the increased risk for and the
signs and symptoms of GI bleeding [see Warnings and Precautions (5.2)].
Hepatotoxicity
Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue,
lethargy, pruritus, diarrhea, jaundice, right upper quadrant tenderness, and "flu-like" symptoms).
If these occur, instruct patients to stop Ambator Diclofenac Patch and seek immediate medical
therapy [see Warnings and Precautions (5.3)].
Heart Failure and Edema
Advise patients to be alert for the symptoms of congestive heart failure including shortness of
breath, unexplained weight gain, or edema and to contact their healthcare provider if such symptoms
occur [see Warnings and Precautions (5.5)].
Anaphylactic Reactions
Inform patients of the signs of an anaphylactic reaction (e.g., difficulty breathing, swelling of
the face or throat). Instruct patients to seek immediate emergency help if these occur [see
Contraindications (4) and Warnings and Precautions (5.7)].
Serious Skin Reactions
Advise patients to stop Ambator Diclofenac Patch immediately if they develop any type of rash and
to contact their healthcare provider as soon as possible [see Warnings and Precautions (5.9)].
Female Fertility
Advise females of reproductive potential who desire pregnancy that NSAIDs, including AMBATOR
DICLOFENAC PATCH, may be associated with a reversible delay in ovulation [see Use in Specific
Populations (8.3)]
Fetal Toxicity
Inform pregnant women to avoid use of Ambator Diclofenac Patch and other NSAIDs starting at 30
weeks gestation because of the risk of the premature closing of the fetal ductus arteriosus [see
Warnings and Precautions (5.10) and Use in Specific Populations (8.1)].
Avoid Concomitant Use of NSAIDs
Inform patients that the concomitant use of Ambator Diclofenac Patch 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 Ambator Diclofenac Patch until they
talk to their healthcare provider [see Drug Interactions (7)].
Eye Exposure
Instruct patients to avoid contact of Ambator Diclofenac Patch with the eyes and mucosa. Advise
patients that if eye contact occurs, immediately wash out the eye with water or saline and consult
a physician if irritation persists for more than an hour [see Warnings and Precautions (5.15)].
Special Application Instructions
• Instruct patients that, if Ambator Diclofenac Patch begins to peel-off, the edges of the patch
may be taped down. If problems with adhesion persist, patients may overlay the patch with a mesh
netting sleeve, where appropriate (e.g. to secure patches applied to ankles, knees, or elbows). The
mesh netting sleeve (e.g. Curad® Hold Tite™, Surgilast® Tubular Elastic Dressing) must allow air to
pass through and not be occlusive (non-breathable).

• Instruct patients not to apply Ambator Diclofenac Patch to non-intact or damaged skin resulting
from any etiology e.g. exudative dermatitis, eczema, infected lesion, burns or wounds.
• Instruct patients not to wear a Ambator Diclofenac Patch when bathing or showering.
• Instruct patients to wash hands after applying, handling or removing the patch.

Manufactured for:
7T Pharma
Los Angeles, CA 90064
For more information, call 7T Pharma at 1-800-941-2848. Revised: September, 2017
Ambator Diclofenac Patch is a registered trademark of the manufacturer.

This Medication Guide has been approved by the U.S. Food and Drug Administration. Issued or
Revised: Sept, 2017

Medication Guide for Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

What is the most important information I should know about medicines called Nonsteroidal
Anti-inflammatory Drugs (NSAIDs)? NSAIDs can cause serious side effects, including:

• Increased risk of a heart attack or stroke that can lead to death. This risk may happen early
in treatment and may increase:
o with increasing doses of NSAIDs
o with longer use of NSAIDs

Do not take NSAIDs right before or after a heart surgery called a "coronary artery bypass graft
(CABG)." Avoid taking NSAIDs after a recent heart attack, unless your healthcare provider tells you
to. You may have an increased risk of another heart attack if you take NSAIDs after a recent heart
attack.
Increased risk of bleeding, ulcers, and tears (perforation) of the esophagus (tube leading from
the mouth to the stomach), stomach and intestines:
o anytime during use
o without warning symptoms
o that may cause death

The risk of getting an ulcer or bleeding increases with:
o past history of stomach ulcers, or stomach or intestinal bleeding with use of NSAIDs
o taking medicines called "corticosteroids", "anticoagulants", "SSRIs", or "SNRIs"

o increasing doses of NSAIDs
o longer use of NSAIDs
o smoking
o drinking alcohol

o older age
o poor health
o advanced liver disease
o bleeding problems

NSAIDs should only be used:

o exactly as prescribed
o at the lowest dose possible for your treatment
o for the shortest time needed

What are NSAIDs?

NSAIDs are used to treat pain and redness, swelling, and heat (inflammation) from medical
conditions such as different types of arthritis, menstrual cramps, and other types of short-term
pain.

Who should not take NSAIDs? Do not take NSAIDs:

• if you have had an asthma attack, hives, or other allergic reaction with aspirin or any other
NSAIDs.
• right before or after heart bypass surgery.

Before taking NSAIDS, 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. Talk to your healthcare provider if you are considering
taking NSAIDs during pregnancy. You should not take NSAIDs after 29 weeks of pregnancy.
• are breastfeeding or plan to breast feed.

Tell your healthcare provider about all of the medicines you take, including prescription or
over-the-counter medicines, vitamins or herbal supplements. NSAIDs and some other medicines can
interact with each other and cause serious side effects. Do not start taking any new medicine
without talking to your healthcare provider first.
What are the possible side effects of NSAIDs? NSAIDs can cause serious side effects, including:
See "What is the most important information I should know about medicines called Nonsteroidal
Anti-inflammatory Drugs (NSAIDs)?

• new or worse high blood pressure
• heart failure
• liver problems including liver failure
• kidney problems including kidney failure
• low red blood cells (anemia)
• life-threatening skin reactions
• life-threatening allergic reactions
• Other side effects of NSAIDs include: stomach pain, constipation, diarrhea, gas, heartburn,
nausea, vomiting, and dizziness.

Get emergency help right away if you get any of the following symptoms:

• shortness of breath or trouble breathing
• chest pain
• weakness in one part or side of your body

• slurred speech
• swelling of the face or throat

Stop taking your NSAID and call your healthcare provider right away if you get any of the following
symptoms:

• nausea
• more tired or weaker than usual
• diarrhea
• itching
• your skin or eyes look yellow
• indigestion or stomach pain
• flu-like symptoms

• vomit blood
• there is blood in your bowel movement or it is black and sticky like tar
• unusual weight gain
• skin rash or blisters with fever
• swelling of the arms, legs, hands and feet

If you take too much of your NSAID, call your healthcare provider or get medical help right away.
These are not all the possible side effects of NSAIDs. For more information, ask your healthcare
provider or pharmacist about NSAIDs.
Call your doctor for medical advice about side effects. You may report side effects to FDA at
1-800-FDA-1088.

Other information about NSAIDs

• Aspirin is an NSAID but it does not increase the chance of a heart attack. Aspirin can cause
bleeding in the brain, stomach, and intestines. Aspirin can also cause ulcers in the stomach and
intestines.
• Some NSAIDs are sold in lower doses without a prescription (over-the counter). Talk to your
healthcare provider before using over-the-

counter NSAIDs for more than 10 days.

General information about the safe and effective use of NSAIDs

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do
not use NSAIDs for a condition for which it was not prescribed. Do not give NSAIDs to other people,
even if they have the same symptoms that you have. It may harm them.
If you would like more information about NSAIDs, talk with your healthcare provider. You can ask
your pharmacist or healthcare provider for information about NSAIDs that is written for health
professionals.

PRINCIPAL DISPLAY PANEL - 10 Patch Carton
NDC 70645-212-01
Ambator Diclofenac Patch®
(diclofenac sodium topical patch) 1.5%
Rx Only
10 PATCHES (12.5 CM X 8.5 CM EACH)
Dispense with enclosed Medication Guide

Change patch once every 12 hours.
Fold used patches so that the adhesive side sticks to itself and safely discard used patches where
children and pets cannot get to them.

Ambator Diclofenac Patch 
diclofenac sodium patch
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:70645-212
Route of Administration TOPICAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
DICLOFENAC SODIUM (DICLOFENAC) DICLOFENAC SODIUM 1 g  in 10 mL
Inactive Ingredients
Ingredient Name Strength
WATER  
DIHYDROXYALUMINUM AMINOACETATE  
GLYCERIN  
KAOLIN  
METHYLPARABEN  
POLYACRYLIC ACID (8000 MW)  
POLYSORBATE 80  
PROPYLPARABEN  
PROPYLENE GLYCOL  
POVIDONE, UNSPECIFIED  
SODIUM POLYACRYLATE (8000 MW)  
TARTARIC ACID  
TITANIUM DIOXIDE  
Packaging
# Item Code Package Description
1 NDC:70645-212-01 10 PATCH in 1 PACKAGE
1 8 mL in 1 PATCH
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
unapproved drug other 12/15/2017
Labeler - 7T Pharma LLC (080220022)
 
7T Pharma LLC