LIDOVIX DELAYED RELEASE- lidocaine, diclofenac sodium

United States - English - NLM (National Library of Medicine)

Buy It Now

Active ingredient:
DICLOFENAC SODIUM (UNII: QTG126297Q) (DICLOFENAC - UNII:144O8QL0L1)
Available from:
Primary Pharmaceuticals, Inc.
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Carefully consider the potential benefits and risks of diclofenac sodium delayed-release tablets and other treatment options before deciding to use diclofenac. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals ( see WARNINGS; Gastrointestinal Bleeding, Ulceration, and Perforation ). Diclofenac is indicated: - For relief of the signs and symptoms of osteoarthritis - For relief of the signs and symptoms of rheumatoid arthritis - For acute or long-term use in the relief of signs and symptoms of ankylosing spondylitis Diclofenac sodium delayed-release tablets are 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; Anaphylactic Reactions, Serious Skin Reactions ). - History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSA
Product summary:
75 mg -– white to off-white, biconvex, round shaped, unscored (imprinted on one side), supplied in bottles of 60 Bottles of 60 ..................................................................NDC 61442-103-60 Store at room temperature 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Protect from moisture. Dispense in tight container (USP). Manufactured by: Carlsbad Tech Carlsbad, CA 92008 USA Revised: 05/2016 Lidocaine patch 5% is available as the following: Carton of 30 patches, packaged into individual child-resistant envelopes. NDC 0591-3525-30 Store at 20o to 25oC (68o to 77oF) [See USP Controlled Room Temperature]. For more information, call Actavis at 1-800-272-5525. Manufactured by: Actavis Laboratories UT, Inc. Salt Lake City, UT 84108 USA
Authorization status:
unapproved drug other
Authorization number:
0591-3525-30, 72275-708-77

LIDOVIX DELAYED RELEASE- lidocaine, diclofenac sodium

Primary Pharmaceuticals, Inc.

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.

----------

Medication Guide for Nonsteroidal

Anti-Inflammatory Drugs (NSAIDs)

What is the most important information I should know about medicines called Non-Steroidal Anti-

Inflammatory Drugs (NSAIDs)?

NSAIDs can cause serious side effects, including:

Increased risk of heart attack or stroke that can lead to death.This risk may happen early in treatment

and may increase:

with increasing doses of NSAIDS

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:

anytime during use

without warning symptoms

that may cause death

The risk of getting an ulcer or bleeding increases with:

past history of stomach ulcers, or intestinal bleeding with use of NSAIDs

taking medicines called “corticosteroids”, “anticoagulants”, “SSRIs” or “SNRIs”

increasing doses of NSAIDs

longer use of NSAIDs

smoking

drinking alcohol

older age

poor health

advanced liver disease

bleeding problems

NSAIDs should only be used:

exactly as prescribed

at the lowest dose possible for your treatment

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 have any of the following symptoms:

shortness of breath

chest pain

slurred speech or trouble breathing

swelling of the face or throat

weakness in one part or side of your body

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

vomit blood

there is blood in your bowel movement or it is

diarrhea

itching

your skin or eyes look yellow

indigestion or stomach pain

flu-like symptoms

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 medicine 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.

For more information, go to www.carlsbadtech. com or call 1-855-397-9777

This Medication Guide has been approved by the U.S. Food and Drug Administration

CTI-1 MG Rev. G 05/2016

Revised: 8/2019

Document Id: 8f896469-4df2-599c-e053-2a95a90ac924

34391-3

Set id: 8f880f4b-07b1-3650-e053-2995a90a5549

Version: 1

Effective Time: 20190807

Primary Pharmaceuticals, Inc.

LIDOVIX DELAYED RELEASE- lidocaine, diclofenac sodium

Primary Pharmaceuticals, Inc.

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.

----------

Lidovix

Delayed-Release Tablets USP

Rx only

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).

Diclofenac sodium delayed-release tablets are contraindicated in the setting of coronary

artery bypass graft (CABG) surgery (see CONTRAINDICATIONS, WARNINGS).

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).

DESCRIPTION

Diclofenac sodium delayed-release tablets is a benzene-acetic acid derivative. Diclofenac sodium is a

white or slightly yellowish crystalline powder and is sparingly soluble in water at 25°C. The chemical

name is 2-[(2,6-dichlorophenyl)amino] benzeneacetic acid, monosodium salt. The molecular weight is

318.14. Its molecular formula is C

NNaO

, and it has the following structural formula

The inactive ingredients in diclofenac sodium delayed-release tablets include: hydroxypropyl

methylcellulose, lactose monohydrate, magnesium stearate, methacrylic acid copolymer,

microcrystalline cellulose, polyethylene glycol, povidone, propylene glycol, sodium starch glycolate,

talc, titanium dioxide, triethyl citrate.

CLINICAL PHARMACOLOGY

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.

Pharmacokinetics

Absorption

Diclofenac is 100% absorbed after oral administration compared to IV administration as measured by

urine recovery. However, due to first-pass metabolism, only about 50% of the absorbed dose is

systemically available (see Table 1). Food has no significant effect on the extent of diclofenac

absorption. However, there is usually a delay in the onset of absorption of 1 to 4.5 hours and a

reduction in peak plasma levels of <20%.

Table 1. Pharmacokinetic Parameters for Diclofenac

PK Parameter

Normal Healthy Adults (20-48 years)

Mean

Coefficient of Mean

Variation (%)

Absolute

Bioavailability (%)

[N = 7]

(hr) [N = 56]

Oral Clearance (CL/F;

mL/min) [N = 56]

Renal Clearance

(% unchanged drug in

urine) [N = 7]

<1

Apparent Volume of

Distribution (V/F; L/kg)

[N = 56]

Terminal Half-life (hr)

[N = 56]

Distribution

The apparent volume of distribution (V/F) of diclofenac sodium is 1.4 L/kg.

Diclofenac is more than 99% bound to human serum proteins, primarily to albumin. Serum protein

binding is constant over the concentration range (0.15-105 mcg/ml) achieved with recommended doses.

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 CYP2C9.

Both diclofenac and its oxidative metabolites undergo glucuronidation or sulfation followed by biliary

excretion. Acylglucuronidation mediated by UGT2B7 and oxidation mediated by CYP2C8 may also play

a role in diclofenac metabolism. CYP3A4 is responsible for the formation of minor metabolites, 5-

hydroxy- and 3'-hydroxy-diclofenac. In patients with renal dysfunction, peak concentrations of

metabolites 4'-hydroxy- and 5-hydroxydiclofenac were approximately 50% and 4% of the parent

compound after single oral dosing compared to 27% and 1% in normal healthy subjects.

Excretion

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. Because renal elimination is not a

significant pathway of elimination for unchanged diclofenac, dosing adjustment in patients with mild to

moderate renal dysfunction is not necessary. The terminal half-life of unchanged diclofenac is

approximately 2 hours.

Special Populations

Pediatric: The pharmacokinetics of diclofenac has not been investigated in pediatric patients.

Race: Pharmacokinetic differences due to race have not been identified.

Hepatic Impairment: Hepatic metabolism accounts for almost 100% of diclofenac elimination, so

patients with hepatic disease may require reduced doses of diclofenac compared to patients with normal

hepatic function.

Renal Impairment: Diclofenac pharmacokinetics has been investigated in subjects with renal

insufficiency. No differences in the pharmacokinetics of diclofenac have been detected in studies of

patients with renal impairment. In patients with renal impairment (inulin clearance 60-90, 30-60, and <30

mL/min; N=6 in each group), AUC values and elimination rate were comparable to those in healthy

subjects.

Drug Interactions Studies

Voriconazole: When co-administered with voriconazole (inhibitor of CYP2C9, 2C19 and 3A4 enzyme),

the C

and AUC of diclofenac increased by 114% and 78%, respectively ( see PRECAUTIONS;

Drug Interactions).

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 2 for clinically significant drug interactions of NSAIDs with aspirin ( see

PRECAUTIONS; Drug Interactions).

INDICATIONS AND USAGE

Carefully consider the potential benefits and risks of diclofenac sodium delayed-release tablets and

other treatment options before deciding to use diclofenac. Use the lowest effective dose for the

shortest duration consistent with individual patient treatment goals ( see WARNINGS; Gastrointestinal

Bleeding, Ulceration, and Perforation).

Diclofenac is indicated:

For relief of the signs and symptoms of osteoarthritis

For relief of the signs and symptoms of rheumatoid arthritis

For acute or long-term use in the relief of signs and symptoms of ankylosing spondylitis

CONTRAINDICATIONS

Diclofenac sodium delayed-release tablets are 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; Anaphylactic Reactions, Serious Skin Reactions).

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; Anaphylactic Reaction, Exacerbation of Asthma Related to Aspirin Sensitivity).

In the setting of coronary artery bypass graft (CABG) surgery ( see Warnings; Cardiovascular

Thrombotic Events).

WARNINGS

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;

Gastrointestinal Bleeding, Ulceration, and Perforation).

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).

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 reinfection, 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 diclofenac sodium delayed-release tablets in patients with a recent MI unless the

benefits are expected to outweigh the risk of recurrent CV thrombotic events. If diclofenac sodium

delayed-release tablets are used in patients with a recent MI, monitor patients for signs of cardiac

ischemia.

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 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 use 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

diclofenac sodium delayed-release tablets 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 PRECAUTIONS; Drug Interactions).

Hepatotoxicity

In clinical trials of 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 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.), diclofenac 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 diclofenac immediately, and perform a clinical evaluation of the

patient.

To minimize the potential risk for an adverse liver related event in patients treated with diclofenac, use

the lowest effective dose for the shortest duration possible. Exercise caution when prescribing

diclofenac with concomitant drugs that are known to be potentially hepatotoxic (e.g., acetaminophen,

antibiotics, anti-epileptics).

Hypertens ion

NSAIDs, including diclofenac, 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, thiazides diuretics, or loop diuretics may have

impaired response to these therapies when taking NSAIDs. (see PRECAUTIONS; Drug Interactions) .

Monitor blood pressure (BP) during the initiation of NSAID treatment and throughout the course of

therapy.

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

PRECAUTIONS; Drug Interactions).

Avoid the use of diclofenac in patients with severe heart failure unless the benefits are expected to

outweigh the risk of worsening heart failure. If diclofenac is used in patients with severe heart failure,

monitor patients for signs of worsening heart failure.

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 a 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 diclofenac in patients

with advanced renal disease. The renal effects of diclofenac 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 diclofenac. Monitor

renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia

during use of diclofenac (see PRECAUTIONS; Drug Interactions). Avoid the use of diclofenac in

patients with advanced renal disease unless the benefits are expected to outweigh the risk of worsening

renal function. If diclofenac 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.

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,

WARNINGS; Exacerbation of Asthma Related to Aspirin Sensitivity).

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, diclofenac is contraindicated in patients with this form of

aspirin sensitivity (see CONTRAINDICATIONS). When diclofenac is used in patients with preexisting

asthma (without known aspirin sensitivity), monitor patients for changes in the signs and symptoms of

asthma.

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 diclofenac at the first appearance of skin rash or any other sign

of hypersensitivity. Diclofenac is contraindicated in patients with previous serious skin reactions to

NSAIDs (see CONTRAINDICATIONS).

Premature Closure of Fetal Ductus Arteriosus

Diclofenac may cause premature closure of the fetal ductus arteriosus. Avoid use of NSAIDs,

including diclofenac, in pregnant women starting at 30 weeks of gestation (third trimester) (see

PRECAUTIONS; Pregnancy).

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 diclofenac, has

any signs or symptoms of anemia, monitor hemoglobin or hematocrit.

NSAIDs, including diclofenac, 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 PRECAUTIONS; Drug

Interactions).

PRECAUTIONS

General

Diclofenac sodium delayed-release tablets cannot be expected to substitute for corticosteroids or to

treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease

exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a

decision is made to discontinue corticosteroids and the patient should be observed closely for any

evidence of adverse effects, including adrenal insufficiency and exacerbation of symptoms of arthritis.

The pharmacological activity of diclofenac in reducing fever and inflammation may diminish the utility

of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.

Information for Patients

Advise the patient to read the FDA-approved patient labeling (Medication Guide) that accompanies each

prescription dispensed. Inform patients, families, or their caregivers of the following information

before initiating therapy with diclofenac 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

healthcare provider immediately (see WARNINGS; Cardiovascular Thrombotic Events).

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 the signs and symptoms of GI

bleeding (see WARNING; Gastrointestinal Bleeding, Ulceration, and Perforation).

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 diclofenac and seek immediate medical therapy (see WARNINGS; Hepatotoxicity).

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; Heart Failure and Edema).

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 WARNINGS;

Anaphylactic Reactions).

Serious Skin Reactions

Advise patients to stop diclofenac immediately if they develop any type of rash and contact their

healthcare provider as soon as possible (see WARNINGS; Serious Skin Reactions).

Female Fertility

Advise females of reproductive potential who desire pregnancy that NSAIDs, including diclofenac,

may be associated with a reversible delay in ovulation (see PRECAUTIONS; Carcinogenesis,

Mutagenesis, Impairment of Fertility).

Fetal Toxicity

Inform pregnant women to avoid use of diclofenac and other NSAIDs, starting at 30 weeks gestation

because of the risk of the premature closure of the fetal ductus arteriosus (see WARNINGS; Premature

Closure of Fetal Ductus Arteriosus).

Avoid Concomitant Use of NSAIDs

Inform patients that the concomitant use of diclofenac 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; Gastrointestinal Bleeding, Ulceration, and Perforation and Drug

Interactions). 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 diclofenac until they talk to their

healthcare provider (see PRECAUTIONS; Drug Interactions).

Masking of Inflammation and Fever

The pharmacological activity of diclofenac in reducing inflammation, and possibly fever, may diminish

the utility of diagnostic signs in detecting infections.

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; Gastrointestinal Bleeding, Ulceration and Perforation, and Hepatotoxicity).

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 diclofenac 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

PRECAUTIONS; Hematological Toxicity).

As pirin

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; Gastrointestinal Bleeding, Ulceration, and Perforation) .

Intervention:

Concomitant use of diclofenac and analgesic doses of aspirin is not

generally recommended because of the increased risk of bleeding ( see

PRECAUTIONS: Hematological Toxicity).

Diclofenac 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 diclofenac and

ACE-inhibitors, ARBs, or betablockers, monitor blood pressure to

ensure that the desired blood pressure is obtained.

During concomitant use of diclofenac 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; Renal Toxicity and Hyperkalemia).

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 diclofenac with diuretics, observe patients for

signs of worsening renal function, in addition to assuring diuretic efficacy

including antihypertensive effects ( see WARNINGS; Renal Toxicity and

Hyperkalemia).

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 diclofenac 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 diclofenac 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 diclofenac and methotrexate, monitor patients for

methotrexate toxicity.

Cyclosporine

Clinical Impact:

Concomitant use of diclofenac and cyclosporine may increase

cyclosporine's nephrotoxicity.

Intervention:

During concomitant use of diclofenac 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; Gastrointestinal Bleeding, Ulceration,

and Perforation).

Intervention:

The concomitant use of diclofenac with other NSAIDs or salicylates is not

recommended.

Pemetrexed

Clinical Impact:

Concomitant use of diclofenac and pemetrexed may increase the risk of

pemetrexedassociated myelosuppression, renal, and GI toxicity (see the

pemetrexed prescribing information).

Intervention:

During concomitant use of diclofenac and pemetrexed, in patients with renal

impairment

whose

creatinine

clearance

ranges

from

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.

CYP2C9 Inhibitors or Inducers:

Clinical Impact:

Diclofenac is metabolized by cytochrome P450 enzymes, predominantly by

CYP2C9. Co-administration of diclofenac with CYP2C9 inhibitors (e.g.

voriconazole) may enhance the exposure and toxicity of diclofenac whereas

co-administration with CYP2C9 inducers (e.g. rifampin) may lead to

compromised efficacy of diclofenac.

Intervention:

A dosage adjustment may be warranted when diclofenac is administered with

CYP2C9 inhibitors or inducers ( see CLINICAL PHARMACOLOGY;

Pharmacokinetics).

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Long-term carcinogenicity studies in rats given diclofenac sodium up to 2 mg/kg/day (approximately 0.1

times maximum recommended human dose (MRHD) of diclofenac, 200 mg/day, based on body surface

area (BSA) comparison ) have revealed no significant increases in tumor incidence. A 2-year

carcinogenicity study conducted in mice employing diclofenac sodium at doses up to 0.3 mg/kg/day

(approximately 0.007 times the MRHD based on BSA comparison) in males and 1 mg/kg/day

(approximately 0.02 times the MRHD based on BSA comparison) in females did not reveal any

oncogenic potential.

Mutagenesis

Diclofenac sodium did not show mutagenic activity in in vitro point mutation assays in mammalian (mouse

lymphoma) and microbial (yeast, Ames) test systems and was nonmutagenic in several mammalian in vitro

and in vivo tests, including dominant lethal and male germinal epithelial chromosomal studies in mice,

and nucleus anomaly and chromosomal aberration studies in Chinese hamsters.

Impairment of Fertility

Diclofenac sodium administered to male and female rats at 4 mg/kg/day (approximately 0.2 times the

MRHD based on BSA comparison) did not affect fertility.

Based on the mechanism of action, the use of prostaglandin-mediated NSAIDs, including diclofenac,

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 diclofenac, in women who have difficulties conceiving or who are

undergoing investigation of infertility.

Pregnancy

Risk Summary

Use of NSAIDs, including diclofenac, during the third trimester of pregnancy increases the risk of

premature closure of the fetal ductus arteriosus. Avoid use of NSAIDs, including diclofenac, in

pregnant women starting at 30 weeks of gestation (third trimester) (see WARNINGS; Premature Closure

of Fetal Ductus Arterious).

There are no adequate and well-controlled studies of diclofenac 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, no evidence of

teratogenicity was observed in mice, rats, or rabbits given diclofenac during the period of

organogenesis at doses up to approximately 0.5, 0.5, and 1 times, respectively, the maximum

recommended human dose (MRHD) of diclofenac, 200 mg/day, despite the presence of maternal and

fetal toxicity at these doses [see Data] . Based on animal data, prostaglandins have been shown to have

an important role in endometrial vascular permeability, blastocyst implantation, and decasualization. In

animal studies, administration of prostaglandin synthesis inhibitors such as diclofenac, resulted in

increased pre- and post-implantation loss.

Data

Animal Data

Reproductive and developmental studies in animals demonstrated that diclofenac sodium administration

during organogenesis did not produce teratogenicity despite the induction of maternal toxicity and fetal

toxicity in mice at oral doses up to 20 mg/kg/day (approximately 0.5 times the maximum recommended

human dose [MRHD] of diclofenac, 200 mg/day, based on body surface area (BSA) comparison), and in

rats and rabbits at oral doses up to 10 mg/kg/day (approximately 0.5 and 1 times, respectively, the

MRHD based on BSA comparison). In a study in which pregnant rats were orally administered 2 or 4

mg/kg diclofenac (0.1 and 0.2 times the MRHD based on BSA) from Gestation Day 15 through Lactation

Day 21, significant maternal toxicity (peritonitis, mortality) was noted. These 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, rats, and humans.

Labor or Delivery

There are no studies on the effects of diclofenac during labor or delivery. In animal studies, NSAIDS,

including diclofenac, inhibit prostaglandin synthesis, cause delayed parturition, and increase the

incidence of stillbirth.

Nursing Mothers

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 diclofenac and any

potential adverse effects on the breastfed infant from the diclofenac 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).

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

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; Cardiovascular Thrombotic Events, Gastrointestinal

Bleeding, Ulceration, and Perforation, Hepatotoxicity, Renal Toxicity and Hyperkalemia, PRECAUTIONS;

Laboratory Monitoring ) .

Diclofenac is known to be substantially excreted by the kidney, and the risk of adverse reactions to this

drug may be greater in patients with impaired renal function. Because elderly patients are more likely to

have decreased renal function, care should be taken in dose selection, and it may be useful to monitor

renal function (See CLINICAL PHARMACOLOGY, ADVERSE REACTIONS).

ADVERSE REACTIONS

The following adverse reactions are discussed in greater detail in other sections of the labeling:

Cardiovascular Thrombotic Events (see WARNINGS)

GI Bleeding, Ulceration and Perforation (see WARNINGS)

Hepatotoxicity (see WARNINGS)

Hypertension (see WARNINGS)

Heart Failure and Edema (see WARNINGS)

Renal Toxicity and Hyperkalemia (see WARNINGS)

Anaphylactic Reactions (see WARNINGS)

Serious Skin Reactions (see WARNINGS)

Hematologic Toxicity (see WARNINGS)

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 to rates in the clinical trials of another drug

and may not reflect the rates observed in practice.

In patients taking diclofenac sodium delayed-release tablets, or other NSAIDs, the most frequently

reported adverse experiences occurring in approximately 1%-10% of patients are:

Gastrointestinal experiences including: abdominal pain, constipation, diarrhea, dyspepsia, flatulence,

gross bleeding/perforation, heartburn, nausea, GI ulcers (gastric/duodenal) and vomiting.

Abnormal renal function, anemia, dizziness, edema, elevated liver enzymes, headaches, increased

bleeding time, pruritus, rashes and tinnitus.

Additional adverse experiences reported occasionally include:

Body as a Whole: fever, infection, sepsis

Cardiovascular System: congestive heart failure, hypertension, tachycardia, syncope

Digestive System: dry mouth, esophagitis, gastric/peptic ulcers, gastritis, gastrointestinal bleeding,

glossitis, hematemesis, hepatitis, jaundice

Hemic and Lymphatic System: ecchymosis, eosinophilia, leukopenia,

melena, purpura, rectal bleeding, stomatitis, thrombocytopenia

Metabolic and Nutritional: weight changes

Nervous System: anxiety, asthenia, confusion, depression, dream abnormalities, drowsiness, insomnia,

malaise, nervousness, paresthesia, somnolence, tremors, vertigo

Respiratory System: asthma, dyspnea

Skin and Appendages: alopecia, photosensitivity, sweating increased

Special Senses: blurred vision

Urogenital System: cystitis, dysuria, hematuria, interstitial nephritis, oliguria/polyuria, proteinuria, renal

failure

Other adverse reactions, which occur rarely are:

Body as a Whole: anaphylactic reactions, appetite changes, death

Cardiovascular System: arrhythmia, hypotension, myocardial infarction, palpitations, vasculitis

Digestive System: colitis, eructation, fulminant hepatitis with and without jaundice, liver failure, liver

necrosis, pancreatitis

Hemic and Lymphatic System: agranulocytosis, hemolytic anemia, aplastic anemia, lymphadenopathy,

Hemic and Lymphatic System: agranulocytosis, hemolytic anemia, aplastic anemia, lymphadenopathy,

pancytopenia

Metabolic and Nutritional: hyperglycemia

Nervous System: convulsions, coma, hallucinations, meningitis

Respiratory System: respiratory depression, pneumonia

Skin and Appendages: angioedema, toxic epidermal necrolysis, erythema multiforme, exfoliative

dermatitis, Stevens-Johnson syndrome, urticaria

Special Senses: conjunctivitis, hearing impairment

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; Cardiovascular Thrombotic Events, Gastrointestinal

Bleeding, Ulceration, and Perforation, Hypertension, Renal Toxicity and Hyperkalemia) .

Manage patients with symptomatic and supportive care following an NSAID overdosage. There are no

specific antidotes. Consider emesis and/or activated charcoal (60 to 100 grams in adults, 1 to 2 grams

per kg of body weight in pediatric patients) and/or osmotic cathartic in symptomatic patients seen within

four hours of ingestion or in patients with a large overdose (5 to 10 times the recommended dosage).

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).

DOSAGE AND ADMINISTRATION

Carefully consider the potential benefits and risks of diclofenac sodium delayed-release tablets and

other treatment options before deciding to use diclofenac. Use the lowest effective dose for the

shortest duration consistent with individual patient treatment goals (see WARNINGS; Gastrointestinal

Bleeding, Ulceration, and Perforation) .

After observing the response to initial therapy with diclofenac, the dose and frequency should be

adjusted to suit an individual patient's needs.

For the relief of osteoarthritis, the recommended dosage is 100-150 mg/day in divided doses (50 mg

twice a day or three times a day, or 75 mg twice a day).

For the relief of rheumatoid arthritis, the recommended dosage is 150-200 mg/day in divided doses (50

mg three times a day. or four times a day, or 75 mg twice a day.).

For the relief of ankylosing spondylitis, the recommended dosage is 100-125 mg/day, administered as

25 mg four times a day, with an extra 25-mg dose at bedtime if necessary.

HOW SUPPLIED

Diclofenac sodium delayed-release tablets

75 mg -– white to off-white, biconvex, round shaped, unscored (imprinted

on one side), supplied in

bottles of 60

Bottles of 60 ..................................................................NDC 61442-103-60

Store at room temperature 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C

(59°F to 86°F) [see USP Controlled Room Temperature].

Protect from moisture.

Dispense in tight container (USP).

Manufactured by:

Carlsbad Tech

Carlsbad, CA 92008 USA

Revised: 05/2016

Medication Guide for Nonsteroidal

Anti-Inflammatory Drugs (NSAIDs)

What is the most important information I should know about medicines called Non-Steroidal

Anti-Inflammatory Drugs (NSAIDs)?

NSAIDs can cause serious side effects, including:

Increased risk of heart attack or stroke that can lead to death.This risk may happen early in

treatment and may increase:

with increasing doses of NSAIDS

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:

anytime during use

without warning symptoms

that may cause death

The risk of getting an ulcer or bleeding increases with:

past history of stomach ulcers, or intestinal bleeding with use of NSAIDs

taking medicines called “corticosteroids”, “anticoagulants”, “SSRIs” or “SNRIs”

increasing doses of NSAIDs

longer use of NSAIDs

smoking

drinking alcohol

older age

poor health

advanced liver disease

bleeding problems

NSAIDs should only be used:

exactly as prescribed

at the lowest dose possible for your treatment

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 have any of the following symptoms:

shortness of breath

chest pain

slurred speech or trouble breathing

swelling of the face or throat

weakness in one part or side of your body

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 medicine 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.

For more information, go to www.carlsbadtech. com or call 1-855-397-9777

This Medication Guide has been approved by the U.S. Food and Drug Administration

CTI-1 MG Rev. G 05/2016

Lidocaine Patch 5%

Revised: February 2015

Rx Only

Lidocaine Description

Lidocaine patch 5% is comprised of an adhesive material containing 5% lidocaine, which is applied to a

white non-woven polyethylene terephthalate (PET) material backing and covered with a transparent PET

release liner. The release liner is removed prior to application to the skin. The size of the patch is 10

cm x 14 cm.

Lidocaine is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl), has an

octanol:water partition ratio of 43 at pH 7.4, and has the following structure:

Each adhesive patch contains 700 mg of lidocaine (50 mg per gram adhesive) in an aqueous base. It also

contains the following inactive ingredients: glycerin, D-sorbitol, propylene glycol, polyvinyl alcohol,

urea, sodium polyacrylate, carboxymethylcellulose sodium, gelatin, polyacrylic acid, kaolin, tartaric

acid, dihydroxyaluminum aminoacetate, methylparaben, propylparaben, and edetate disodium.

Lidocaine Clinical Pharmacology

Pharmacodynamics

Lidocaine is an amide-type local anesthetic agent and is suggested to stabilize neuronal membranes by

inhibiting the ionic fluxes required for the initiation and conduction of impulses.

The penetration of lidocaine into intact skin after application of lidocaine patch is sufficient to produce

an analgesic effect, but less than the amount necessary to produce a complete sensory block.

Pharmacokinetics

Abs orption:

The amount of lidocaine systemically absorbed from lidocaine patch is directly related to both the

duration of application and the surface area over which it is applied. In a pharmacokinetic study, three

lidocaine patches were applied over an area of 420 cm2 of intact skin on the back of normal volunteers

for 12 hours. Blood samples were withdrawn for determination of lidocaine concentration during the

application and for 12 hours after removal of patches. The results are summarized in Table 1.

When lidocaine patch is used according to the recommended dosing instructions, only 3 ± 2% of the

dose applied is expected to be absorbed. At least 95% (665 mg) of lidocaine will remain in a used

patch. Mean peak blood concentration of lidocaine is about 0.13 mcg/mL (about 1/10 of the therapeutic

concentration required to treat cardiac arrhythmias). Repeated application of three patches

simultaneously for 12 hours (recommended maximum daily dose), once per day for three days, indicated

that the lidocaine concentration does not increase with daily use. The mean plasma pharmacokinetic

profile for the 15 healthy volunteers is shown in Figure 1.

Figure 1 Mean lidocaine blood concentrations after three consecutive daily applications of three

lidocaine patches simultaneously for 12 hours per day in healthy volunteers (n = 15).

Dis tribution:

When lidocaine is administered intravenously to healthy volunteers, the volume of distribution is 0.7 to

2.7 L/kg (mean 1.5 ± 0.6 SD, n=15). At concentrations produced by application of lidocaine patch,

lidocaine is approximately 70% 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.

Metabolis m:

It is not known if lidocaine 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. A minor metabolite,

2, 6-xylidine, has unknown pharmacologic activity but is carcinogenic in rats. The blood concentration

of this metabolite is negligible following application of lidocaine patch 5%. Following intravenous

administration, MEGX and GX concentrations in serum range from 11 to 36% and from 5 to 11% of

lidocaine concentrations, respectively.

Excretion:

Lidocaine and its metabolites are excreted by the kidneys. Less than 10% of lidocaine is excreted

unchanged. The half-life of lidocaine elimination from the plasma following IV administration is 81 to

149 minutes (mean 107 ± 22 SD, n = 15). The systemic clearance is 0.33 to 0.90 L/min (mean 0.64 ±

0.18 SD, n = 15).

Lidocaine Clinical Trials

Single-dose treatment with lidocaine patch was compared to treatment with vehicle patch (without

lidocaine), and to no treatment (observation only) in a double-blind, crossover clinical trial with 35 post-

herpetic neuralgia patients. Pain intensity and pain relief scores were evaluated periodically for 12

hours. Lidocaine patch performed statistically better than vehicle patch in terms of pain intensity from 4

to 12 hours.

Multiple-dose, two-week treatment with lidocaine patch was compared to vehicle patch (without

lidocaine) in a double-blind, crossover clinical trial of withdrawal-type design conducted in 32 patients,

who were considered as responders to the open-label use of lidocaine patch prior to the study. The

constant type of pain was evaluated but not the pain induced by sensory stimuli (dysesthesia).

Statistically significant differences favoring lidocaine patch were observed in terms of time to exit

from the trial (14 versus 3.8 days at p-value <0.001), daily average pain relief, and patient’s preference

of treatment. About half of the patients also took oral medication commonly used in the treatment of

post-herpetic neuralgia. The extent of use of concomitant medication was similar in the two treatment

groups.

Lidocaine Indications and Usage

Lidocaine patch 5% is indicated for relief of pain associated with post-herpetic neuralgia. It should be

applied only to intact skin.

Contraindications

Lidocaine patch 5% is contraindicated in patients with a known history of sensitivity to local anesthetics

of the amide type, or to any other component of the product.

Lidoacaine Warnings

Accidental Exposure in Children

Even a used lidocaine patch contains a large amount of lidocaine (at least 665 mg). The potential exists

for a small child or a pet to suffer serious adverse effects from chewing or ingesting a new or used

lidocaine patch, although the risk with this formulation has not been evaluated. It is important for patients

to store and dispose of lidocaine patch 5% out of the reach of children, pets and others. (See

HANDLING AND DISPOSAL)

Excessive Dosing

Excessive dosing by applying lidocaine patch 5% to larger areas or for longer than the recommended

wearing time could result in increased absorption of lidocaine and high blood concentrations, leading to

serious adverse effects (see ADVERSE REACTIONS, Systemic Reactions). Lidocaine toxicity could

be expected at lidocaine blood concentrations above 5 mcg/mL. The blood concentration of lidocaine is

determined by the rate of systemic absorption and elimination. Longer duration of application,

application of more than the recommended number of patches, smaller patients, or impaired elimination

may all contribute to increasing the blood concentration of lidocaine. With recommended dosing of

lidocaine patch 5%, the average peak blood concentration is about 0.13 mcg/mL, but concentrations

higher than 0.25 mcg/mL have been observed in some individuals.

Lidocaine Precaution

General

Hepatic Disease: Patients with severe hepatic disease are at greater risk of developing toxic blood

concentrations of lidocaine, because of their inability to metabolize lidocaine normally.

Allergic Reactions: Patients allergic to para-aminobenzoic acid derivatives (procaine, tetracaine,

benzocaine, etc.) have not shown cross sensitivity to lidocaine. However, lidocaine patch 5% should be

used with caution in patients with a history of drug sensitivities, especially if the etiologic agent is

uncertain.

Non-intact Skin: Application to broken or inflamed skin, although not tested, may result in higher blood

concentrations of lidocaine from increased absorption. Lidocaine patch 5% is only recommended for

use on intact skin.

External Heat Sources: Placement of external heat sources, such as heating pads or electric blankets,

over lidocaine patch 5% is not recommended as this has not been evaluated and may increase plasma

lidocaine levels.

Eye Exposure: The contact of lidocaine patch 5% with eyes, although not studied, should be avoided

based on the findings of severe eye irritation with the use of similar products in animals. If eye contact

occurs, immediately wash out the eye with water or saline and protect the eye until sensation returns.

Drug Interactions

Antiarrhythmic Drugs: Lidocaine patch 5% should be used with caution in patients receiving Class I

antiarrhythmic drugs (such as tocainide and mexiletine) since the toxic effects are additive and

potentially synergistic.

Local Anesthetics: When lidocaine patch 5% is used concomitantly with other products containing local

anesthetic agents, the amount absorbed from all formulations must be considered.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis: A minor metabolite, 2,6-xylidine, has been found to be carcinogenic in rats. The blood

concentration of this metabolite is negligible following application of lidocaine patch 5%.

Mutagenesis: Lidocaine HCl is not mutagenic in Salmonella/mammalian microsome test nor clastogenic

in chromosome aberration assay with human lymphocytes and mouse micronucleus test.

Impairment of Fertility: The effect of lidocaine patch 5% on fertility has not been studied.

Pregnancy

Teratogenic Effects: Pregnancy Category B. Lidocaine patch 5% has not been studied in pregnancy.

Reproduction studies with lidocaine have been performed in rats at doses up to 30 mg/kg

subcutaneously and have revealed no evidence of harm to the fetus due to lidocaine. There are,

however, no adequate and well-controlled studies in pregnant women. Because animal reproduction

studies are not always predictive of human response, lidocaine patch 5% should be used during

pregnancy only if clearly needed.

Labor and Delivery

Lidocaine patch 5% has not been studied in labor and delivery. Lidocaine is not contraindicated in labor

and delivery. Should lidocaine patch 5% be used concomitantly with other products containing

lidocaine, total doses contributed by all formulations must be considered.

Nursing Mothers

Lidocaine patch 5% has not been studied in nursing mothers. Lidocaine is excreted in human milk, and

the milk:plasma ratio of lidocaine is 0.4. Caution should be exercised when lidocaine patch 5% is

administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Lidocaine Adverse Reactions

Application Site Reactions

During or immediately after treatment with lidocaine patch 5%, the skin at the site of application may

develop blisters, bruising, burning sensation, depigmentation, dermatitis, discoloration, edema,

erythema, exfoliation, irritation, papules, petechia, pruritus, vesicles, or may be the locus of abnormal

sensation. These reactions are generally mild and transient, resolving spontaneously within a few

minutes to hours.

Allergic Reactions

Allergic and anaphylactoid reactions associated with lidocaine, although rare, can occur. They are

characterized by angioedema, bronchospasm, dermatitis, dyspnea, hypersensitivity, laryngospasm,

pruritus, shock, and urticaria. If they occur, they should be managed by conventional means. The

detection of sensitivity by skin testing is of doubtful value.

Other Adverse Events

Due to the nature and limitation of spontaneous reports in postmarketing surveillance, causality has not

been established for additional reported adverse events including:

Asthenia, confusion, disorientation, dizziness, headache, hyperesthesia, hypoesthesia, lightheadedness,

metallic taste, nausea, nervousness, pain exacerbated, paresthesia, somnolence, taste alteration,

vomiting, visual disturbances such as blurred vision, flushing, tinnitus, and tremor.

Systemic (Dose-Related) Reactions

Systemic adverse reactions following appropriate use of lidocaine patch 5% are unlikely, due to the

small dose absorbed (see CLINICAL PHARMACOLOGY, Pharmacokinetics). Systemic adverse

effects of lidocaine are similar in nature to those observed with other amide local anesthetic agents,

including CNS excitation and/or depression (light-headedness, 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. Cardiovascular manifestations may include bradycardia,

hypotension and cardiovascular collapse leading to arrest.

To report SUSPECTED ADVERSE REACTIONS, contact Actavis at 1-800-272-5525 or FDA at 1-

800-FDA-1088 or www.fda.gov/medwatch for voluntary reporting of adverse reactions.

Lidocaine Overdose

Lidocaine overdose from cutaneous absorption is rare, but could occur. If there is any suspicion of

lidocaine overdose (see ADVERSE REACTIONS, Systemic Reactions), drug blood concentration

should be checked. The management of overdose includes close monitoring, supportive care, and

symptomatic treatment. Dialysis is of negligible value in the treatment of acute overdose with lidocaine.

In the absence of massive topical overdose or oral ingestion, evaluation of symptoms of toxicity should

include consideration of other etiologies for the clinical effects, or overdosage from other sources of

lidocaine or other local anesthetics.

The oral LD50 of lidocaine HCl is 459 (346 to 773) mg/kg (as the salt) in non-fasted female rats and

214 (159 to 324) mg/kg (as the salt) in fasted female rats, which are equivalent to roughly 4000 mg and

2000 mg, respectively, in a 60 to 70 kg man based on the equivalent surface area dosage conversion

factors between species.

Lidocaine Dosage & Administration

Apply lidocaine patch 5% to intact skin to cover the most painful area. Apply the prescribed number of

patches (maximum of 3), only once for up to 12 hours within a 24-hour period. Patches may be cut into

smaller sizes with scissors prior to removal of the release liner. (See HANDLING AND DISPOSAL)

Clothing may be worn over the area of application. Smaller areas of treatment are recommended in a

debilitated patient, or a patient with impaired elimination.

If irritation or a burning sensation occurs during application, remove the patch(es) and do not reapply

until the irritation subsides.

When lidocaine patch 5% is used concomitantly with other products containing local anesthetic agents,

the amount absorbed from all formulations must be considered.

Lidocaine patch 5% may not stick if it gets wet. Avoid contact with water, such as bathing, swimming or

showering.

Handling and Disposal

Hands should be washed after the handling of lidocaine patch 5%, and eye contact with lidocaine patch

5% should be avoided. Do not store patch outside the sealed envelope. Apply immediately after

removal from the protective envelope. Fold used patches so that the adhesive side sticks to itself and

safely discard used patches or pieces of cut patches where children and pets cannot get to them.

Lidocaine patch 5% should be kept out of the reach of children.

Lidocaine How Supplied

Lidocaine patch 5% is available as the following:

Carton of 30 patches, packaged into individual child-resistant envelopes.

NDC 0591-3525-30

Store at 20o to 25oC (68o to 77oF) [See USP Controlled Room Temperature].

For more information, call Actavis at 1-800-272-5525.

Manufactured by:

Actavis Laboratories UT, Inc.

Salt Lake City, UT 84108 USA

Principal Display Panel

LIDOVIX DELAYED RELEASE

lidocaine, diclofenac sodium kit

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:72275-70 8

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:72275-70 8 -77

1 in 1 CARTON

0 8 /0 1/20 19

1

1 in 1 BOX

1

1 in 1 BOTTLE; Type 1: Co nvenience Kit o f Co -Package

Quantity of Parts

Part #

Package Quantity

Total Product Quantity

Pa rt 1

1 BOTTLE

Pa rt 2

1 POUCH

Part 1 of 2

DICLOFENAC SODIUM DELAYED RELEASE

diclofenac sodium tablet, delayed release

Product Information

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

DICLO FENAC SO DIUM (UNII: QTG126 29 7Q) (DICLOFENAC - UNII:144O8 QL0 L1)

DICLOFENAC SODIUM

75 mg

Inactive Ingredients

Ingredient Name

Stre ng th

FERRO SO FERRIC O XIDE (UNII: XM0 M8 7F357)

LACTO SE MO NO HYDRATE (UNII: EWQ57Q8 I5X)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

CELLULO SE, MICRO CRYSTALLINE (UNII: OP1R32D6 1U)

SHELLAC (UNII: 46 N10 7B71O)

PO VIDO NE (UNII: FZ9 8 9 GH9 4E)

SO DIUM STARCH GLYCO LATE TYPE A PO TATO (UNII: 58 56 J3G2A2)

TALC (UNII: 7SEV7J4R1U)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

HYPRO MELLO SES (UNII: 3NXW29 V3WO)

METHACRYLIC ACID - METHYL METHACRYLATE CO PO LYMER ( 1:1) (UNII: 74G4R6 TH13)

PO LYETHYLENE GLYCO L 2 0 0 0 (UNII: HAF0 412YIT)

Product Characteristics

Color

white

S core

no sco re

S hap e

ROUND

S iz e

9 mm

Flavor

Imprint Code

CTI;10 2

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

6 0 in 1 BOTTLE; Type 1: Co nvenience Kit o f Co -Package

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 7518 5

11/13/19 9 8

Part 2 of 2

LIDOCAINE

lidocaine patch

Product Information

Ite m Code (Source )

NDC:0 59 1-3525

Route of Administration

TOPICAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

LIDO CAINE (UNII: 9 8 PI20 0 9 8 7) (LIDOCAINE - UNII:9 8 PI20 0 9 8 7)

LIDOCAINE

50 mg in 1 g

Inactive Ingredients

Ingredient Name

Stre ng th

PO LYVINYL ALCO HO L, UNSPECIFIED (UNII: 532B59 J9 9 0 )

UREA (UNII: 8 W8 T178 47W)

SO RBITO L (UNII: 50 6 T6 0 A25R)

PRO PYLENE GLYCO L (UNII: 6 DC9 Q16 7V3)

WATER (UNII: 0 59 QF0 KO0 R)

GLYCERIN (UNII: PDC6 A3C0 OX)

GELATIN, UNSPECIFIED (UNII: 2G8 6 QN327L)

TARTARIC ACID (UNII: W48 8 8 I119 H)

DIHYDRO XYALUMINUM AMINO ACETATE (UNII: DO250 MG0 W6 )

METHYLPARABEN (UNII: A2I8 C7HI9 T)

EDETATE DISO DIUM (UNII: 7FLD9 1C8 6 K)

KAO LIN (UNII: 24H4NWX5CO)

PRO PYLPARABEN (UNII: Z8 IX2SC1OH)

CARBO XYMETHYLCELLULO SE SO DIUM (UNII: K6 79 OBS311)

Packag ing

#

Item Code

Package Description

Marketing Start

Date

Marketing End

Date

1

NDC:0 59 1-

3525-30

30 in 1 CARTON

1

1 g in 1 POUCH; Type 2: Prefilled Drug Delivery Device/System

(syringe, patch, etc.)

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA20 0 6 75

0 9 /15/20 13

Marketing Information

Primary Pharmaceuticals, Inc.

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

unappro ved drug o ther

0 8 /0 1/20 19

Labeler -

Primary Pharmaceuticals, Inc. (066126126)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Actavis Labo rato ries UT, Inc

0 79 58 9 8 8 0

ma nufa c ture (0 59 1-3525)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Rainbo w Go ld

8 0 0 6 9 5152

re pa c k(72275-70 8 )

Revised: 8/2019

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