NAPROXEN- naproxen tablet

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Active ingredient:
NAPROXEN (UNII: 57Y76R9ATQ) (NAPROXEN - UNII:57Y76R9ATQ)
Available from:
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Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Naproxen Naproxen tablets and naproxen sodium tablets are indicated for: The relief of the signs and symptoms of: • rheumatoid arthritis • osteoarthritis • ankylosing spondylitis • Polyarticular Juvenile Idiopathic Arthritis Naproxen tablets, and naproxen sodium tablets are contraindicated in the following patients: • Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to naproxen 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)] 8.1 Pregnancy Risk Summary Use of NSAIDs, including naproxen tablets, or naproxen sodium tablets, during the third trimester of pregnancy increases the
Product summary:
Naproxen Tablets USP, 250 mg: circular, light orange colored, flat, uncoated tablets, engraved with ‘G’ and ‘32’ on either side of break line on one side and ‘250’ on the other side. Packaged in light-resistant bottles of 100 and 500. 100’s (bottle): 500’s (bottle): Naproxen Tablets USP, 375 mg: oval, light orange colored, biconvex, uncoated tablets, engraved with ‘G 32’ on one side and ‘375’ on the other side. Packaged in light-resistant bottles of 100 and 500. 100’s (bottle): 500’s (bottle): Naproxen Tablets USP, 500 mg: capsule shaped, light orange colored, uncoated tablets, debossed with ‘G’ and ‘32’ on either side of break line on one side and ‘500’ on the other side. Packaged in light-resistant bottles of 30, 50, 100 and 500. 30’s (bottle): 50’s (bottle): 100’s (bottle): 500’s (bottle): Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Dispense in well-closed containers. Naproxen Sodium Tablets USP, 275 mg: blue, oval, film-coated tablets with ‘G 0’ engraved on one side and ‘275’ engraved on the other side. Packaged in bottles of 100 and 500 100’s (bottle): 500’s (bottle): Naproxen Sodium Tablets USP, 550 mg: blue colored, modified capsule shaped, biconvex, film-coated tablets, engraved with ‘G’ and ‘0’ on either side of break line and break line on the other side. Packaged in bottles of 100 and 500. 100’s (bottle): Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Dispense in well-closed containers.
Authorization status:
Abbreviated New Drug Application
Authorization number:
61919-376-20

NAPROXEN- naproxen tablet

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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 a 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:

any time 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 stomach or intestinal bleeding with use of NSAIDs

taking medicines

older age

increasing doses of NSAIDs

poor health

longer use of NSAIDs

advanced liver disease

smoking

bleeding problems

drinking alcohol

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 get any of the following symptoms:

shortness of breath or trouble breathing

slurred speech

chest pain

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

vomit blood

more tired or weaker than usual

there is blood in your bowel movement or it is black and sticky like tar

diarrhea

unusual weight gain

itching

skin rash or blisters with fever

your skin or eyes look yellow

swelling of the arms, legs, hands and feet

indigestion or stomach pain

flu-like symptoms

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.

Manufactured by:

Glenmark Pharmaceuticals Ltd., INDIA

[Glenmark Logo]

Manufactured for:

Glenmark Pharmaceuticals Inc., USA

Mahwah, NJ 07430

Questions? 1 (888)721-7115

www.glenmarkpharma.com/usa

May 2017

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

Revised: 8/2019

Document Id: 90b6672d-05f6-a6c3-e053-2a95a90a49f0

34391-3

Set id: 90b6672d-05f5-a6c3-e053-2a95a90a49f0

Version: 1

Effective Time: 20190822

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NAPROXEN- naproxen tablet

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NAPROXEN

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)].

Naproxen tablets and naproxen sodium tablets are contraindicated in the setting of coronary artery

bypass graft (CABG) surgery [see Contraindications (4), 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)].

Naproxen Naproxen tablets and naproxen sodium tablets are indicated for:

The relief of the signs and symptoms of:

rheumatoid arthritis

osteoarthritis

ankylosing spondylitis

Polyarticular Juvenile Idiopathic Arthritis

2.1 General Dosing Instructions

Carefully consider the potential benefits and risks of naproxen tablets and naproxen sodium tablets and

other treatment options before deciding to use naproxen tablets and naproxen sodium tablets. Use the

lowest effective dose for the shortest duration consistent with individual patient treatment goals [see

Warnings and Precautions (5)].

After observing the response to initial therapy with naproxen tablets or naproxen sodium tablets, the

dose and frequency should be adjusted to suit an individual patient’s needs.

Naproxen-containing products such as naproxen and naproxen sodium tablets, and other naproxen

products should not be used concomitantly since they all circulate in the plasma as the naproxen anion.

2.2 Rheumatoid Arthritis, Osteoarthritis and Ankylosing Spondylitis

The recommended dosages of naproxen tablets, naproxen tablets, and naproxen sodium tablets are

shown in Table 1.

Table 1: Recommended dosages for naproxen tablets, and naproxen sodium tablets

Naproxen tablets

250 mg (one half tablet)

500 mg

twice daily

Naproxen sodium tablets

275 mg (one half tablet)

550 mg (naproxen 500 mg with 50 mg sodium)

twice daily

During long-term administration, the dose of naproxen may be adjusted up or down depending on the

clinical response of the patient. A lower daily dose may suffice for long-term administration. The

morning and evening doses do not have to be equal in size and the administration of the drug more

frequently than twice daily is not necessary.

The morning and evening doses do not have to be equal in size and administration of the drug more

frequently than twice daily does not generally make a difference in response.

In patients who tolerate lower doses well, the dose may be increased to naproxen 1500 mg/day for

limited periods of up to 6 months when a higher level of anti-inflammatory/analgesic activity is

required. When treating such patients with naproxen 1500 mg/day, the physician should observe

sufficient increased clinical benefits to offset the potential increased risk.

2.3 Polyarticular Juvenile Idiopathic Arthritis

Naproxen solid-oral dosage forms may not allow for the flexible dose titration needed in pediatric

patients with polyarticular juvenile idiopathic arthritis. A liquid formulation may be more appropriate

for weight-based dosing and due to the need for dose flexibility in children.

In pediatric patients, doses of 5 mg/kg/day produced plasma levels of naproxen similar to those seen in

adults taking 500 mg of naproxen [see Clinical Pharmacology (12)]. The recommended total daily dose

of naproxen is approximately 10 mg/ kg given in 2 divided doses. Dosing with naproxen tablets is not

appropriate for children weighing less than 50 kilograms.

2.4 Management of Pain, Primary Dysmenorrhea, and Acute Tendonitis and Bursitis

The recommended starting dose of naproxen sodium tablets is 550 mg followed by 550 mg every 12

hours or 275 mg (one half of a 550 mg tablet) every 6 to 8 hours as required. The initial total daily dose

should not exceed 1375 mg (two and one-half tablets) of naproxen sodium. Thereafter, the total daily

dose should not exceed 1100 mg of naproxen sodium. Because the sodium salt of naproxen is more

rapidly absorbed, naproxen sodium tablets is recommended for the management of acute painful

conditions when prompt onset of pain relief is desired. Naproxen tablets may also be used. The

recommended starting dose of naproxen tablets is 500 mg followed by 250 mg (one half of a 500 mg

naproxen tablet) every 6 to 8 hours as required. The total daily dose should not exceed 1250 mg of

naproxen.

2.5 Acute Gout

The recommended starting dose is 750 mg (one and one-half tablets) of naproxen tablets followed by

250 mg (one-half tablet) every 8 hours until the attack has subsided. Naproxen sodium tablets may also

be used at a starting dose of 825 mg (one and one-half tablets) followed by 275 mg (one-half tablet)

every 8 hours.

2.6 Non-Interchangeability with Other Formulations of Naproxen

Different dose strengths and formulations (e.g., tablets, suspension) of naproxen are not

interchangeable. This difference should be taken into consideration when changing strengths or

formulations.

Naproxen Tablets USP, 250 mg: circular, light orange colored, flat, uncoated tablets, engraved with ‘G’

and ‘32’ on either side of break line on one side and ‘250’ on the other side.

Naproxen Tablets USP, 375 mg: oval, light orange colored, biconvex, uncoated tablets, engraved with

‘G 32’ on one side and ‘375’ on the other side.

Naproxen Tablets USP, 500 mg: capsule shaped, light orange colored, uncoated tablets, debossed with

‘G’ and ‘32’ on either side of break line on one side and ‘500’ on the other side.

Naproxen Sodium Tablets USP, 275 mg: blue, oval, film-coated tablets with ‘G 0’ engraved on one side

and ‘275’ engraved on the other side.

Naproxen Sodium Tablets USP, 550 mg: blue colored, modified capsule shaped, biconvex, film-coated

tablets, engraved with ‘G’ and ‘0’ on either side of break line and break line on the other side.

Naproxen tablets, and naproxen sodium tablets are contraindicated in the following patients:

Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to naproxen 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)]

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 naproxen, 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 to 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 naproxen tablets and naproxen sodium tablets in patients with a recent MI unless the

benefits are expected to outweigh the risk of recurrent CV thrombotic events. If naproxen tablets and

naproxen sodium tablets are used in patients with a recent MI, monitor patients for signs of cardiac

ischemia.

5.2 Gastrointestinal Bleeding, Ulceration, and Perforation

NSAIDs, including naproxen 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 to 6 months, and in about 2% to 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

naproxen Naproxen tablets and naproxen sodium 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 Drug Interactions (7)].

5.3 Hepatotoxicity

Elevations of ALT or AST (three or more times the upper limit of normal [ULN]) have been reported in

approximately 1% of NSAID-treated patients in clinical trials. In addition, rare, sometimes fatal, cases

of severe hepatic injury, including fulminant hepatitis, liver necrosis, and hepatic failure have been

reported.

Elevations of ALT or AST (less than three times ULN) may occur in up to 15% of patients treated with

NSAIDs including naproxen.

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 naproxen tablets or naproxen sodium tablets immediately, and

perform a clinical evaluation of the patient.

5.4 Hypertension

NSAIDs, including naproxen tablets, and naproxen sodium tablets, can lead to new onset of hypertension

or worsening of pre-existing 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 naproxen 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 naproxen tablets, or naproxen sodium tablets in patients with severe heart failure

unless the benefits are expected to outweigh the risk of worsening heart failure. If naproxen tablets, or

naproxen sodium tablets is used in patients with severe heart failure, monitor patients for signs of

worsening heart failure.

Since each naproxen sodium tablet contains 50 mg of sodium (about 2 mEq per each 500 mg of

naproxen), this should be considered in patients whose overall intake of sodium must be severely

restricted.

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 naproxen tablets, or

naproxen sodium tablets in patients with advanced renal disease. The renal effects of naproxen tablets,

or naproxen sodium tablets may hasten the progression of renal dysfunction in patients with preexisting

renal disease.

Correct volume status in dehydrated or hypovolemic patients prior to initiating naproxen tablets, or

naproxen sodium tablets. Monitor renal function in patients with renal or hepatic impairment, heart

failure, dehydration, or hypovolemia during use of naproxen tablets, and naproxen sodium tablets [see

Drug Interactions (7)]. Avoid the use of naproxen tablets, and naproxen sodium tablets in patients with

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

function. If naproxen tablets, or naproxen sodium tablets 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

Naproxen has been associated with anaphylactic reactions in patients with and without known

hypersensitivity to naproxen 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, naproxen tablets, and naproxen sodium tablets are

contraindicated in patients with this form of aspirin sensitivity [see

Contraindications (4)]. When naproxen tablets, or naproxen sodium tablets 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 naproxen, 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 naproxen tablets, or naproxen sodium tablets at the first

appearance of skin rash or any other sign of hypersensitivity. Naproxen tablets and naproxen sodium

tablets are contraindicated in patients with previous serious skin reactions to NSAIDs [see

Contraindications (4)].

5.10 Premature Closure of Fetal Ductus Arteriosus

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

naproxen tablets, and naproxen sodium tablets, 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 naproxen

tablets, or naproxen sodium tablets has any signs or symptoms of anemia, monitor hemoglobin or

hematocrit.

NSAIDs, including naproxen tablets, and naproxen sodium tablets, may increase the risk of bleeding

events. Co-morbid conditions such as coagulation disorders or concomitant use of warfarin and 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 naproxen tablets, and naproxen sodium tablets in reducing inflammation,

and possibly fever, may diminish the utility of diagnostic signs in detecting infections.

5.13 Long-Term Use and 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)].

Patients with initial hemoglobin values of 10g or less who are to receive long-term therapy should have

hemoglobin values determined periodically.

Because of adverse eye findings in animal studies with drugs of this class, it is recommended that

ophthalmic studies be carried out if any change or disturbance in vision occurs.

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 to rates in the clinical trials of another drug

and may not reflect the rates observed in practice.

Adverse reactions reported in controlled clinical trials in 960 patients treated for rheumatoid arthritis

or osteoarthritis are listed below. In general, reactions in patients treated chronically were reported 2 to

10 times more frequently than they were in short-term studies in the 962 patients treated for mild to

moderate pain or for dysmenorrhea. The most frequent complaints reported related to the

gastrointestinal tract.

A clinical study found gastrointestinal reactions to be more frequent and more severe in rheumatoid

arthritis patients taking daily doses of 1500 mg naproxen compared to those taking 750 mg naproxen.

In controlled clinical trials with about 80 pediatric patients and in well-monitored, open-label studies

with about 400 pediatric patients with polyarticular juvenile idiopathic arthritis treated with naproxen,

the incidence of rash and prolonged bleeding times were greater, the incidence of gastrointestinal and

central nervous system reactions were about the same, and the incidence of other reactions were lower

in pediatric patients than in adults.

In patients taking naproxen in clinical trials, the most frequently reported adverse experiences in

approximately 1% to 10% of patients were:

Gastrointestinal (GI) Experiences, including: heartburn*, abdominal pain*, nausea*, constipation*,

diarrhea, dyspepsia, stomatitis

Central Nervous System: headache*, dizziness*, drowsiness*, lightheadedness, vertigo

Dermatologic: pruritus (itching)*, skin eruptions*, ecchymoses*, sweating, purpura

Special Senses: tinnitus*, visual disturbances, hearing disturbances

Cardiovascular: edema*, palpitations

General: dyspnea*, thirst

*Incidence of reported reaction between 3% and 9%. Those reactions occurring in less than 3% of the

patients are unmarked.

In patients taking NSAIDs, the following adverse experiences have also been reported in approximately

1% to 10% of patients.

Gastrointestinal (GI) Experiences, including: flatulence, gross bleeding/perforation, GI ulcers

(gastric/duodenal), vomiting

General: abnormal renal function, anemia, elevated liver enzymes, increased bleeding time, rashes

The following are additional adverse experiences reported in <1% of patients taking naproxen during

clinical trials.

Gastrointestinal: pancreatitis, vomiting

Hepatobiliary: jaundice

Hemic and Lymphatic: melena, thrombocytopenia, agranulocytosis

Nervous System: inability to concentrate

Dermatologic: skin rashes

6.2 Postmarketing Experience

The following adverse reactions have been identified during post approval use of naproxen. Because

these reactions are reported voluntarily from a population of uncertain size, it is not always possible to

reliably estimate their frequency or establish a causal relationship to drug exposure.

The following are additional adverse experiences reported in <1% of patients taking naproxen during

clinical trials and through postmarketing reports. Those adverse reactions observed through

postmarketing reports are italicized.

Body as a Whole: anaphylactoid reactions, angioneurotic edema, menstrual disorders, pyrexia (chills

and fever)

Cardiovascular: congestive heart failure, vasculitis, hypertension, pulmonary edema

Gastrointestinal: inflammation, bleeding (sometimes fatal, particularly in the elderly), ulceration,

perforation and obstruction of the upper or lower gastrointestinal tract. Esophagitis, stomatitis,

hematemesis, colitis, exacerbation of inflammatory bowel disease (ulcerative colitis, Crohn’s disease).

Hepatobiliary: abnormal liver function tests, hepatitis (some cases have been fatal)

Hemic and Lymphatic: eosinophilia, leucopenia, granulocytopenia, hemolytic anemia, aplastic anemia

Metabolic and Nutritional: hyperglycemia, hypoglycemia

Nervous System: depression, dream abnormalities, insomnia, malaise, myalgia, muscle weakness,

aseptic meningitis, cognitive dysfunction, convulsions

Respiratory: eosinophilic pneumonitis, asthma

Dermatologic: alopecia, urticaria, toxic epidermal necrolysis, erythema multiforme, erythema nodosum,

fixed drug eruption, lichen planus, pustular reaction, systemic lupus erythematoses, bullous reactions,

including Stevens-Johnson syndrome, photosensitive dermatitis, photosensitivity reactions, including

rare cases resembling porphyria cutanea tarda (pseudoporphyria) or epidermolysis bullosa. If skin

fragility, blistering or other symptoms suggestive of pseudoporphyria occur, treatment should be

discontinued and the patient monitored.

Special Senses: hearing impairment, corneal opacity, papillitis, retrobulbar optic neuritis, papilledema

Urogenital: glomerular nephritis, hematuria, hyperkalemia, interstitial nephritis, nephrotic syndrome,

renal disease, renal failure, renal papillary necrosis, raised serum creatinine

Reproduction (female): infertility

In patients taking NSAIDs, the following adverse experiences have also been reported in <1% of

patients.

Body as a Whole: fever, infection, sepsis, anaphylactic reactions, appetite changes, death

Cardiovascular: hypertension, tachycardia, syncope, arrhythmia, hypotension, myocardial infarction

Gastrointestinal: dry mouth, esophagitis, gastric/peptic ulcers, gastritis, glossitis, eructation

Hepatobiliary: hepatitis, liver failure

Hemic and Lymphatic: rectal bleeding, lymphadenopathy, pancytopenia

Metabolic and Nutritional: weight changes

Nervous System: anxiety, asthenia, confusion, nervousness, paresthesia, somnolence, tremors,

convulsions, coma,

hallucinations

Respiratory: asthma, respiratory depression, pneumonia

Dermatologic: exfoliative dermatitis

Special Senses: blurred vision, conjunctivitis

Urogenital: cystitis, dysuria, oliguria/polyuria, proteinuria

See Table 1 for clinically significant drug interactions with naproxen.

Table 1: Clinically Significant Drug Interactions with naproxen

Drugs That Interfere with Hemostasis

Clinical Impact:

Naproxen and anticoagulants such as warfarin have a synergistic effect on bleeding. The concomitant

use of naproxen and anticoagulants has 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 naproxen tablets, or naproxen sodium tablets 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 naproxen tablets, or naproxen sodium tablets and analgesic doses of aspirin is not

generally recommended because of the increased risk of bleeding [see Warnings and Precautions

(5.11)].

Naproxen tablets, or naproxen sodium tablets are 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 naproxen tablets, or naproxen sodium tablets and ACE-inhibitors, ARBs, or

beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained.

During concomitant use of naproxen tablets, or naproxen sodium tablets 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 naproxen tablets, or naproxen sodium tablets 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 naproxen with digoxin has been reported to increase the serum concentration

and prolong the half-life of digoxin.

Intervention:

During concomitant use of naproxen tablets, or naproxen sodium tablets 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 naproxen tablets, or naproxen sodium tablets 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 naproxen tablets, or naproxen sodium tablets and methotrexate, monitor

patients for methotrexate toxicity.

Cyclosporine

Clinical Impact:

Concomitant use of naproxen tablets, or naproxen sodium tablets and cyclosporine may increase

cyclosporine’s nephrotoxicity.

Intervention:

During concomitant use of naproxen tablets, or naproxen sodium tablets and cyclosporine, monitor

patients for signs of worsening renal function.

NSAIDs and Salicylates

Clinical Impact:

Concomitant use of naproxen 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 naproxen with other NSAIDs or salicylates is not recommended.

Pemetrexed

Clinical Impact:

Concomitant use of naproxen tablets and naproxen sodium tablets and pemetrexed may increase the risk

of pemetrexed-associated myelosuppression, renal, and GI toxicity (see the pemetrexed prescribing

information).

Intervention:

During concomitant use of naproxen tablets and naproxen sodium tablets 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.

Antacids and Sucralfate

Clinical Impact:

Concomitant administration of some antacids (magnesium oxide or aluminum hydroxide) and sucralfate

can delay the absorption of naproxen.

Intervention:

Concomitant administration of antacids such as magnesium oxide or aluminum hydroxide, and sucralfate

with naproxen tablets and naproxen sodium tablets is not recommended. Due to the gastric pH elevating

effects of H2-blockers, sucralfate and intensive antacid therapy, concomitant administration of naproxen

tablets, or naproxen sodium tablets is not recommended.

Cholestyramine

Clinical Impact:

Concomitant administration of cholestyramine can delay the absorption of naproxen.

Intervention:

Concomitant administration of cholestyramine with naproxen tablets, or naproxen sodium tablets is not

recommended.

Probenecid

Clinical Impact:

Probenecid given concurrently increases naproxen anion plasma levels and extends its plasma half-life

significantly.

Intervention:

Patients simultaneously receiving naproxen tablets, or naproxen sodium tablets and probenecid should

be observed for adjustment of dose if required.

Other albumin-bound drugs

Clinical Impact:

Naproxen is highly bound to plasma albumin; it thus has a theoretical potential for interaction with other

albumin-bound drugs such as coumarin-type anticoagulants, sulphonylureas, hydantoins, other NSAIDs,

and aspirin.

Intervention:

Patients simultaneously receiving naproxen tablets, or naproxen sodium tablets and a hydantoin,

sulphonamide or sulphonylurea should be observed for adjustment of dose if required.

Drug/Laboratory Test Interactions

Bleeding times

Clinical Impact:

Naproxen may decrease platelet aggregation and prolong bleeding time.

Intervention:

This effect should be kept in mind when bleeding times are determined.

Porter-Silber test

Clinical Impact:

The administration of naproxen may result in increased urinary values for 17 ketogenic steroids because

of an interaction between the drug and/or its metabolites with m-di-nitrobenzene used in this assay.

Intervention:

Although 17-hydroxy-corticosteroid measurements (Porter-Silber test) do not appear to be artifactually

altered, it is suggested that therapy with naproxen be temporarily discontinued 72 hours before adrenal

function tests are performed if the Porter-Silber test is to be used.

Urinary assays of 5-hydroxy indoleacetic acid (5HIAA)

Clinical Impact:

Naproxen may interfere with some urinary assays of 5-hydroxy indoleacetic acid

(5HIAA).

Intervention:

This effect should be kept in mind when urinary 5-hydroxy indoleacetic acid is determined.

8.1 Pregnancy

Risk Summary

Use of NSAIDs, including naproxen tablets, or naproxen sodium tablets, during the third trimester of

pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Avoid use of NSAIDs,

including naproxen tablets, or naproxen sodium tablets, in pregnant women starting at 30 weeks of

gestation (third trimester).

There are no adequate and well-controlled studies of naproxen tablets or naproxen sodium tablets 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 to 4%

for major malformations, and 15 to 20% for pregnancy loss. In animal reproduction studies in rats,

rabbits, and mice no evidence of teratogenicity or fetal harm when naproxen was administered during the

period of organogenesis at doses 0.13, 0.26, and 0.6 times the maximum recommended human daily

dose of 1500 mg/day, respectively [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 naproxen, resulted in

increased pre-and post-implantation loss.

Clinical Considerations

Labor or Delivery

There are no studies on the effects of naproxen tablets, or naproxen sodium tablets during labor or

delivery. In animal studies, NSAIDS, including naproxen, inhibit prostaglandin synthesis, cause delayed

parturition, and increase the incidence of stillbirth.

Data

Human Data

There is some evidence to suggest that when inhibitors of prostaglandin synthesis are used to delay

preterm labor, there is an increased risk of neonatal complications such as necrotizing enterocolitis,

patent ductus arteriosus, and intracranial hemorrhage. Naproxen treatment given in late pregnancy to

delay parturition has been associated with persistent pulmonary hypertension, renal dysfunction, and

abnormal prostaglandin E levels in preterm infants. Because of the known effects of nonsteroidal anti-

inflammatory drugs on the fetal cardiovascular system (closure of ductus arteriosus), use during

pregnancy (particularly starting at 30-weeks of gestation, or third trimester) should be avoided.

Animal Data

Reproduction studies have been performed in rats at 20 mg/kg/day (0.13 times the maximum

recommended human daily dose of 1500 mg/day based on body surface area comparison), rabbits at 20

mg/kg/day (0.26 times the maximum recommended human daily dose, based on body surface area

comparison), and mice at 170 mg/kg/day (0.6 times the maximum recommended human daily dose based

on body surface area comparison) with no evidence of impaired fertility or harm to the fetus due to the

drug. 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 naproxen, resulted in increased pre-and post-implantation

loss.

8.2 Lactation

Risk Summary

The naproxen anion has been found in the milk of lactating women at a concentration equivalent to

approximately 1% of maximum naproxen concentration in plasma. The developmental and health benefits

of breastfeeding should be considered along with the mother’s clinical need for naproxen tablets, or

naproxen sodium tablets and any potential adverse effects on the breastfed infant from the naproxen

tablets, or naproxen sodium tablets or from the underlying maternal condition.

8.3 Females and Males of Reproductive Potential

Infertility

Females

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

tablets, or naproxen sodium tablets, 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 naproxen tablets or

naproxen sodium tablets, in women who have difficulties conceiving or who are undergoing

investigation of infertility.

8.4 Pediatric Use

Safety and effectiveness in pediatric patients below the age of 2 years have not been established.

Pediatric dosing recommendations for polyarticular juvenile idiopathic arthritis are based on well-

controlled studies [see Dosage and Administration (2)]. There are no adequate effectiveness or dose-

response data for other pediatric conditions, but the experience in polyarticular juvenile idiopathic

arthritis and other use experience have established that single doses of 2.5 to 5 mg/kg as naproxen

suspension, , with total daily dose not exceeding 15 mg/kg/day, are well tolerated in pediatric patients

over 2 years of age.

8.5 Geriatric Use

The hepatic and renal tolerability of long-term naproxen administration was studied in two double-blind

clinical trials involving 586 patients. Of the patients studied, 98 patients were age 65 and older and 10

of the 98 patients were age 75 and older. NAPROXEN was administered at doses of 375 mg twice daily

or 750 mg twice daily for up to 6 months. Transient abnormalities of laboratory tests assessing hepatic

and renal function were noted in some patients, although there were no differences noted in the

occurrence of abnormal values among different age groups.

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 (5.1, 5.2, 5.3, 5.6, 5.13)].

Studies indicate that although total plasma concentration of naproxen is unchanged, the unbound plasma

fraction of naproxen is increased in the elderly. The clinical significance of this finding is unclear,

although it is possible that the increase in free naproxen concentration could be associated with an

increase in the rate of adverse events per a given dosage in some elderly patients. Caution is advised

when high doses are required and some adjustment of dosage may be required in elderly patients. As

with other drugs used in the elderly, it is prudent to use the lowest effective dose.

Experience indicates that geriatric patients may be particularly sensitive to certain adverse effects of

nonsteroidal anti- inflammatory drugs. Elderly or debilitated patients seem to tolerate peptic ulceration

or bleeding less well when these events do occur. Most spontaneous reports of fatal GI events are in

the geriatric population [see Warnings andPrecautions (5.2)].

Naproxen is known to be substantially excreted by the kidney, and the risk of toxic 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 (12.3)]. Geriatric patients may be at a greater risk for the

development of a form of renal toxicity precipitated by reduced prostaglandin formation during

administration of nonsteroidal anti-inflammatory drugs [see Warnings andPrecautions (5.6)].

8.6 Hepatic Impairment

Caution is advised when high doses are required and some adjustment of dosage may be required in

these patients. It is prudent to use the lowest effective dose [see Clinical Pharmacology (12.3)].

8.7 Renal Impairment

Naproxen-containing products are not recommended for use in patients with moderate to severe and

severe renal impairment (creatinine clearance <30 mL/min) [see Warnings andPrecautions (5.6), Clinical

Pharmacology (12.3)].

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)].Because naproxen sodium

may be rapidly absorbed, high and early blood levels should be anticipated. A few patients have

experienced convulsions, but it is not clear whether or not these were drug-related. It is not known what

dose of the drug would be life threatening. [see Warnings andPrecautions (5.1, 5.2, 5.4, 5.6)].

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 overdosage (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).

Naproxen Tablets USP and Naproxen Sodium Tablets USP are nonsteroidal anti-inflammatory drugs

available as follows: Naproxen Tablets USP are available as follows for oral administration:

250 mg: circular, light orange colored, flat, uncoated tablets, engraved with ‘G’ and ‘32’ on either side

of break line on one

side and ‘250’ on the other side.

375 mg: oval, light orange colored, biconvex, uncoated tablets, engraved with ‘G 32’ on one side and

‘375’ on the other side.

500 mg: capsule shaped, light orange colored, uncoated tablets, debossed with ‘G’ and ‘32’ on either

side of break line on one side and ‘500’ on the other side.

The inactive ingredients are microcrystalline cellulose, croscarmellose sodium, iron oxide red, iron

oxide yellow, povidone and magnesium stearate.

Naproxen Sodium Tablets USP are available as follows for oral administration:

275 mg: blue, oval, film-coated tablets with ‘G 0’ engraved on one side and ‘275’ engraved on the other

side.

550 mg: blue colored, modified capsule shaped, biconvex, film-coated tablets, engraved with ‘G’ and

‘0’ on either side of break line and break line on the other side.

The inactive ingredients are croscarmellose sodium, colloidal silicon dioxide, povidone, magnesium

stearate, microcrystalline cellulose and talc. The coating suspension for the naproxen sodium 275 mg

and 550 mg tablet contains hypromellose, titanium dioxide, polyethylene glycol, FD&C blue#2, and iron

oxide red.

Naproxen, USP is a propionic acid derivative related to the arylacetic acid group of nonsteroidal anti-

inflammatory drugs. The chemical names for naproxen, USP and naproxen sodium, USP are (S)-6-

methoxy-α-methyl-2-naphthaleneacetic acid and (S)-6methoxy-α-methyl-2-naphthaleneacetic acid,

sodium salt, respectively. Naproxen, USP has a molecular weight of 230.26 and a molecular formula of

C14H14O3. Naproxen sodium, USP has a molecular weight of 252.23 and a molecular formula of

C14H13NaO3. Naproxen, USP and naproxen sodium, USP have the following structures, respectively:

[Structural Formula]

Naproxen, USP is an odorless, white to off-white crystalline substance. It is lipid-soluble, practically

insoluble in water at low pH and freely soluble in water at high pH. The octanol/water partition

coefficient of naproxen at pH 7.4 is 1.6 to 1.8. Naproxen sodium, USP is a white to creamy white,

crystalline solid, freely soluble in water at neutral pH.

12.1 Mechanism of Action

Naproxen has analgesic, anti-inflammatory, and antipyretic properties. Naproxen sodium tablets has been

developed as a more rapidly absorbed formulation of naproxen for use as an analgesic.

The mechanism of action of naproxen, like that of other NSAIDs, is not completely understood but

involves inhibition of cyclooxygenase (COX-1 and COX-2).

Naproxen is a potent inhibitor of prostaglandin synthesis in vitro. Naproxen 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 naproxen is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease

of prostaglandins in peripheral tissues

12.3 Pharmacokinetics

Naproxen is rapidly and completely absorbed from the gastrointestinal tract with an in vivo

bioavailability of 95%. The different dosage forms of naproxen are bioequivalent in terms of extent of

absorption (AUC) and peak concentration (Cmax); however, the products do differ in their pattern of

absorption. These differences between naproxen products are related to both the chemical form of

naproxen used and its formulation. Even with the observed differences in pattern of absorption, the

elimination half-life of naproxen is unchanged across products ranging from 12 to 17 hours. Steady-

state levels of naproxen are reached in 4 to 5 days, and the degree of naproxen accumulation is

consistent with this half-life. This suggests that the differences in pattern of release play only a

negligible role in the attainment of steady-state plasma levels.

Absorption

Naproxen tablets/Naproxen sodium tablets:

After administration of naproxen tablets, peak plasma levels are attained in 2 to 4 hours. After oral

administration of naproxen sodium tablets, peak plasma levels are attained in 1 to 2 hours. The

difference in rates between the two products is due to the increased aqueous solubility of the sodium

salt of naproxen used in naproxen sodium tablets.

Distribution

Naproxen has a volume of distribution of 0.16 L/kg. At therapeutic levels naproxen is greater than 99%

albumin-bound. At doses of naproxen greater than 500 mg/day there is less than proportional increase in

plasma levels due to an increase in clearance caused by saturation of plasma protein binding at higher

doses (average trough Css 36.5, 49.2 and 56.4 mg/L with 500, 1000 and 1500 mg daily doses of

naproxen, respectively). The naproxen anion has been found in the milk of lactating women at a

concentration equivalent to approximately 1% of maximum naproxen concentration in plasma [see Use in

Specific Populations (8.2)].

Elimination

Metabolism

Naproxen is extensively metabolized in the liver to 6-0-desmethyl naproxen, and both parent and

metabolites do not induce metabolizing enzymes. Both naproxen and 6-0-desmethyl naproxen are further

metabolized to their respective acylglucuronide conjugated metabolites.

Excretion

The clearance of naproxen is 0.13 mL/min/kg. Approximately 95% of the naproxen from any dose is

excreted in the urine, primarily as naproxen (<1%), 6-0-desmethyl naproxen (<1%) or their conjugates

(66% to 92%). The plasma half-life of the naproxen anion in humans ranges from 12 to 17 hours. The

corresponding half-lives of both naproxen’s metabolites and conjugates are shorter than 12 hours, and

their rates of excretion have been found to coincide closely with the rate of naproxen clearance from

the plasma. Small amounts, 3% or less of the administered dose, are excreted in the feces. In patients

with renal failure metabolites may accumulate [see Warnings and Precautions (5.6)].

Specific Population

Pediatric:

In pediatric patients aged 5 to 16 years with arthritis, plasma naproxen levels following a 5 mg/kg single

dose of naproxen suspension [see Dosage and Administration (2)] were found to be similar to those

found in normal adults following a 500 mg dose. The terminal half-life appears to be similar in pediatric

and adult patients. Pharmacokinetic studies of naproxen were not performed in pediatric patients younger

than 5 years of age. Pharmacokinetic parameters appear to be similar following administration of

naproxen suspension or tablets in pediatric patients.

Geriatric:

Studies indicate that although total plasma concentration of naproxen is unchanged, the unbound plasma

fraction of naproxen is increased in the elderly, although the unbound fraction is <1% of the total

naproxen concentration. Unbound trough naproxen concentrations in elderly subjects have been reported

to range from 0.12% to 0.19% of total naproxen concentration, compared with 0.05% to 0.075% in

younger subjects.

Hepatic Impairment:

Naproxen pharmacokinetics have not been determined in subjects with hepatic insufficiency.

Chronic alcoholic liver disease and probably other diseases with decreased or abnormal plasma

proteins (albumin) reduce the total plasma concentration of naproxen, but the plasma concentration of

unbound naproxen is increased.

Renal Impairment:

Naproxen pharmacokinetics have not been determined in subjects with renal insufficiency. Given that

naproxen, its metabolites and conjugates are primarily excreted by the kidney, the potential exists for

naproxen metabolites to accumulate in the presence of renal insufficiency. Elimination of naproxen is

decreased in patients with severe renal impairment.

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)]

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

A 2-year study was performed in rats to evaluate the carcinogenic potential of naproxen at rat doses of

8, 16, and 24 mg/kg/day (0.05, 0.1, and 0.16 times the maximum recommended human daily dose

[MRHD] of 1500 mg/day based on a body surface area comparison). No evidence of tumorigenicity

was found.

Mutagenesis

Naproxen tested positive in the in vivo sister chromatid exchange assay for but was not mutagenic in the

in vitro bacterial reverse mutation assay (Ames test).

Impairment of fertility

Male rats were treated with 2, 5, 10, and 20 mg/kg naproxen by oral gavage for 60 days prior to mating

and female rats were treated with the same doses for 14 days prior to mating and for the first 7 days of

pregnancy. There were no adverse effects on fertility noted (up to 0.13 times the MRDH based on body

surface area).

Naproxen has been studied in patients with rheumatoid arthritis, osteoarthritis, polyarticular juvenile

idiopathic arthritis, ankylosing spondylitis, tendonitis and bursitis, and acute gout. Improvement in

patients treated for rheumatoid arthritis was demonstrated by a reduction in joint swelling, a reduction in

duration of morning stiffness, a reduction in disease activity as assessed by both the investigator and

patient, and by increased mobility as demonstrated by a reduction in walking time. Generally, response to

naproxen has not been found to be dependent on age, sex, severity or duration of rheumatoid arthritis.

In patients with osteoarthritis, the therapeutic action of naproxen has been shown by a reduction in joint

pain or tenderness, an increase in range of motion in knee joints, increased mobility as demonstrated by a

reduction in walking time, and improvement in capacity to perform activities of daily living impaired by

the disease.

In a clinical trial comparing standard formulations of naproxen 375 mg twice a day (750 mg a day) vs 750

mg twice a day (1500 mg/day), 9 patients in the 750 mg group terminated prematurely because of

adverse events. Nineteen patients in the 1500 mg group terminated prematurely because of adverse

events. Most of these adverse events were gastrointestinal events.

In clinical studies in patients with rheumatoid arthritis, osteoarthritis, and polyarticular juvenile

idiopathic arthritis, naproxen has been shown to be comparable to aspirin and indomethacin in

controlling the aforementioned measures of disease activity, but the frequency and severity of the

milder gastrointestinal adverse effects (nausea, dyspepsia, heartburn) and nervous system adverse

effects (tinnitus, dizziness, lightheadedness) were less in naproxen-treated patients than in those treated

with aspirin or indomethacin.

In patients with ankylosing spondylitis, naproxen has been shown to decrease night pain, morning

stiffness and pain at rest. In double-blind studies the drug was shown to be as effective as aspirin, but

with fewer side effects.

In patients with acute gout, a favorable response to naproxen was shown by significant clearing of

inflammatory changes (e.g., decrease in swelling, heat) within 24 to 48 hours, as well as by relief of

pain and tenderness.

Naproxen has been studied in patients with mild to moderate pain secondary to postoperative,

orthopedic, postpartum episiotomy and uterine contraction pain and dysmenorrhea. Onset of pain relief

can begin within 1 hour in patients taking naproxen and within 30 minutes in patients taking naproxen

sodium. Analgesic effect was shown by such measures as reduction of pain intensity scores, increase in

pain relief scores, decrease in numbers of patients requiring additional analgesic medication, and delay

in time to remedication. The analgesic effect has been found to last for up to 12 hours.

Naproxen may be used safely in combination with gold salts and/or corticosteroids; however, in

controlled clinical trials, when added to the regimen of patients receiving corticosteroids, it did not

appear to cause greater improvement over that seen with corticosteroids alone. Whether naproxen has a

“steroid-sparing” effect has not been adequately studied. When added to the regimen of patients

receiving gold salts, naproxen did result in greater improvement. Its use in combination with salicylates

is not recommended because there is evidence that aspirin increases the rate of excretion of naproxen

and data are inadequate to demonstrate that naproxen and aspirin produce greater improvement over that

achieved with aspirin alone. In addition, as with other NSAIDs, the combination may result in higher

frequency of adverse events than demonstrated for either product alone.

In 51Cr blood loss and gastroscopy studies with normal volunteers, daily administration of 1000 mg of

naproxen as 1000 mg of naproxen or 1100 mg of naproxen sodium has been demonstrated to cause

statistically significantly less gastric bleeding and erosion than 3250 mg of aspirin.

Three 6-week, double-blind, multicenter studies with naproxen delayed-release (375 or 500 mg twice a

day, n=385) and naproxen (375 or 500 mg twice a day, n=279) were conducted comparing naproxen

delayed-release with naproxen, including 355 rheumatoid arthritis and osteoarthritis patients who had a

recent history of NSAID-related GI symptoms. These studies indicated that naproxen delayed-release

and naproxen showed no significant differences in efficacy or safety and had similar prevalence of

minor GI complaints. Individual patients, however, may find one formulation preferable to the other.

Five hundred and fifty-three patients received naproxen delayed-release during long-term open-label

trials (mean length of treatment was 159 days). The rates for clinically-diagnosed peptic ulcers and GI

bleeds were similar to what has been historically reported for long-term NSAID use.

Naproxen Tablets USP, 250 mg: circular, light orange colored, flat, uncoated tablets, engraved with ‘G’

and ‘32’ on either side of break line on one side and ‘250’ on the other side. Packaged in light-resistant

bottles of 100 and 500.

100’s (bottle):

500’s (bottle):

Naproxen Tablets USP, 375 mg: oval, light orange colored, biconvex, uncoated tablets, engraved with

‘G 32’ on one side and ‘375’ on the other side. Packaged in light-resistant bottles of 100 and 500.

100’s (bottle):

500’s (bottle):

Naproxen Tablets USP, 500 mg: capsule shaped, light orange colored, uncoated tablets, debossed with

‘G’ and ‘32’ on either side of break line on one side and ‘500’ on the other side. Packaged in light-

resistant bottles of 30, 50, 100 and 500.

30’s (bottle):

50’s (bottle):

100’s (bottle):

500’s (bottle):

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [See USP

Controlled Room Temperature]. Dispense in well-closed containers.

Naproxen Sodium Tablets USP, 275 mg: blue, oval, film-coated tablets with ‘G 0’ engraved on one side

and ‘275’ engraved on the other side. Packaged in bottles of 100 and 500

100’s (bottle):

500’s (bottle):

Naproxen Sodium Tablets USP, 550 mg: blue colored, modified capsule shaped, biconvex, film-coated

tablets, engraved with ‘G’ and ‘0’ on either side of break line and break line on the other side. Packaged

in bottles of 100 and 500.

100’s (bottle):

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [See USP

Controlled Room Temperature]. Dispense in well-closed containers.

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 naproxen tablets or naproxen sodium tablets 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 naproxen tablets or naproxen sodium tablets 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 naproxen tablets or naproxen sodium tablets 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 naproxen

tablets or naproxen sodium tablets, 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 naproxen tablets or naproxen sodium tablets 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 naproxen tablets or naproxen sodium tablets 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 naproxen tablets or naproxen sodium

tablets until they talk to their healthcare provider [see Drug Interactions (7)].

Manufactured by:

Glenmark Pharmaceuticals Ltd., INDIA

[Glenmark]

Manufactured for:

Glenmark Pharmaceuticals Inc., USA

Mahwah, NJ 07430

Questions? 1 (888)721-7115 www.glenmarkpharma.com/usa

May 2017

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 a 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:

any time 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 stomach or intestinal bleeding with use of NSAIDs

taking medicines

older age

increasing doses of NSAIDs

poor health

longer use of NSAIDs

advanced liver disease

smoking

bleeding problems

drinking alcohol

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 get any of the following symptoms:

shortness of breath or trouble breathing

slurred speech

chest pain

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

vomit blood

more tired or weaker than usual

there is blood in your bowel movement or it is black and sticky like tar

diarrhea

unusual weight gain

itching

skin rash or blisters with fever

your skin or eyes look yellow

swelling of the arms, legs, hands and feet

indigestion or stomach pain

flu-like symptoms

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.

Manufactured by:

Glenmark Pharmaceuticals Ltd., INDIA

[Glenmark Logo]

Manufactured for:

Glenmark Pharmaceuticals Inc., USA

Mahwah, NJ 07430

Questions? 1 (888)721-7115

www.glenmarkpharma.com/usa

May 2017

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

NAPROXEN

naproxen tablet

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:6 19 19 -376 (NDC:6 8 46 2-19 0 )

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

NAPRO XEN (UNII: 57Y76 R9 ATQ) (NAPROXEN - UNII:57Y76 R9 ATQ)

NAPROXEN

50 0 mg

Inactive Ingredients

Ingredient Name

Stre ng th

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

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

FERRIC O XIDE YELLO W (UNII: EX438 O2MRT)

FERRIC O XIDE RED (UNII: 1K0 9 F3G6 75)

MICRO CRYSTALLINE CELLULO SE (UNII: OP1R32D6 1U)

CRO SCARMELLO SE SO DIUM (UNII: M28 OL1HH48 )

Product Characteristics

Color

o range ((Light o range))

S core

2 pieces

S hap e

CAPSULE

S iz e

16 mm

Flavor

Imprint Code

G;32;50 0

Contains

Dire ct_Rx

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:6 19 19 -376 -20

20 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 8 /22/20 19

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 78 250

0 8 /22/20 19

Labeler -

Direct_Rx (079254320)

Registrant -

Direct_Rx (079254320)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Dire c t_Rx

0 79 254320

re pa c k(6 19 19 -376 )

Revised: 8/2019

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