Naprelan

Name: Naprelan

Indications

NAPRELAN Tablets are indicated for the treatment of:

  • rheumatoid arthritis (RA)
  • osteoarthritis (OA)
  • ankylosing spondylitis (AS)
  • tendinitis, bursitis
  • acute gout
  • primary dysmenorrhea (PD)
  • the relief of mild to moderate pain

[see WARNINGS AND PRECAUTIONS].

Commonly used brand name(s)

In the U.S.

  • Aflaxen
  • Aleve
  • Aleve Arthritis
  • Anaprox
  • Anaprox DS
  • EC Naprosyn
  • Naprelan
  • Naprelan 500
  • Naprelan Dose Card
  • Naprosyn

In Canada

  • Naxen

Available Dosage Forms:

  • Tablet
  • Suspension
  • Tablet, Enteric Coated
  • Tablet, Extended Release
  • Capsule, Liquid Filled
  • Capsule

Therapeutic Class: Analgesic

Pharmacologic Class: NSAID

Chemical Class: Propionic Acid (class)

Uses For Naprelan

Naproxen is a nonsteroidal anti-inflammatory drug (NSAID) used to relieve symptoms of arthritis (osteoarthritis, rheumatoid arthritis, or juvenile arthritis) such as inflammation, swelling, stiffness, and joint pain. Naproxen also helps relieve symptoms of ankylosing spondylitis, which is a type of arthritis that affects the joints in the spine. However, this medicine does not cure arthritis and will help you only as long as you continue to take it.

This medicine may also be used to treat mild to moderate pain, including acute gout and other painful conditions such as bursitis, tendinitis, or menstrual cramps.

This medicine is available only with your doctor's prescription.

Indications and Usage for Naprelan

Naprelan Tablets are indicated for the treatment of:

  • rheumatoid arthritis (RA)
  • osteoarthritis (OA)
  • ankylosing spondylitis (AS)
  • tendinitis, bursitis
  • acute gout
  • primary dysmenorrhea (PD)
  • the relief of mild to moderate pain 

[see Warnings and Precautions (5)].

Dosage Forms and Strengths

Naprelan (naproxen sodium) Controlled-Release Tablets are available as follows:

Naprelan 375: white, capsule-shaped tablet with “N” on one side and “375” on the reverse. Each tablet contains 412.5 mg naproxen sodium equivalent to 375 mg naproxen.

Naprelan 500: white, capsule-shaped tablet with “N” on one side and “500” on the reverse. Each tablet contains 550 mg naproxen sodium equivalent to 500 mg naproxen.

Naprelan 750: white, capsule-shaped tablet with “N” on one side and “750” on the reverse. Each tablet contains 825 mg naproxen sodium equivalent to 750 mg naproxen.

Use in specific populations

Pregnancy

Risk Summary
Use of NSAIDs, including Naprelan, during the third trimester of pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Avoid use of NSAIDs, including Naprelan, in pregnant women starting at 30 weeks of gestation (third trimester).

There are no adequate and well-controlled studies of Naprelan 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, rabbit, 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 1,500 mg/day, respectively.  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 sodium resulted in increased pre- and post-implantation loss.

Clinical Considerations
Labor or Delivery
There are no studies on the effects of Naprelan during labor or delivery. In animal studies, NSAIDS, including naproxen sodium, inhibit prostaglandin synthesis, cause delayed parturition, increase incidence of dystocia 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 effect of drugs of this class on the human fetal cardiovascular system (closure of the ductus arteriosus), use during 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 1,500 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 sodium resulted in increased pre- and post-implantation loss.

Lactation

Risk Summary 
The naproxen anion has been found in the milk of lactating women at a concentration of approximately 1% of that found in the plasma.  The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Naprelan and any potential adverse effects on the breastfed infant from the Naprelan or from the underlying maternal condition.

 Females and Males of Reproductive Potential

Infertility
Females
Based on the mechanism of action, the use of prostaglandin-mediated NSAIDs, including Naprelan, 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 Naprelan, in women who have difficulties conceiving or who are undergoing investigation of infertility.

Pediatric Use

The safety and effectiveness of Naprelan in pediatric populations has 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 and Precautions (5.1, 5.2, 5.3, 5.6, 5.13)].

Naproxen and its metabolites are 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, use caution in this patient population, and it may be useful to monitor renal function [see Clinical Pharmacology (12.3)]

Naprelan Description

Naprelan (naproxen sodium) Controlled-Release Tablets is a nonsteroidal anti-inflammatory drug, available as controlled-release tablets in 375 mg, 500 mg, and 750 mg strengths for oral administration. The chemical name is 2-naphthaleneacetic acid, 6-methoxy-α-methyl-sodium salt, (S)-. The molecular weight is 252.24.  Its molecular formula is C14H13NaO3, and it has the following chemical structure.

Naproxen sodium is an odorless crystalline powder, white to creamy in color. It is soluble in methanol and water. Naprelan Tablets contain 412.5 mg, 550 mg, or 825 mg of naproxen sodium, equivalent to 375 mg, 500 mg, and 750 mg of naproxen, and 37.5 mg, 50 mg, and 75 mg sodium respectively. Each Naprelan Tablet also contains the following inactive ingredients: ammoniomethacrylate copolymer Type A, ammoniomethacrylate copolymer Type B, citric acid, crospovidone, magnesium stearate, methacrylic acid copolymer Type A, microcrystalline cellulose, povidone, and talc. The tablet coating contains hydroxypropyl methylcellulose, polyethylene glycol, and titanium dioxide.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis
A two year study was performed in rats to evaluate the carcinogenic potential of naproxen at doses of 8 mg/kg/day, 16 mg/kg/day, and 24 mg/kg/day (0.05, 0.1, and 0.16 times the maximum recommended human daily dose of 1,500 mg/day based on a body surface area comparison). No evidence of tumorigenicity was found. 

Mutagenesis
Studies to evaluate the mutagenic potential of Naprosyn Suspension have not been completed. 

Impairment of Fertility
Studies to evaluate the impact of naproxen on male or female fertility have not been completed.

How Supplied/Storage and Handling

Naprelan (naproxen sodium) 375 mg, 500 mg, and 750 mg are controlled-release tablets supplied as:

Naprelan 375: white, capsule-shaped tablet with “N” on one side and “375” on the reverse; in bottles of 100; NDC 52427-272-01. Each tablet contains 412.5 mg naproxen sodium equivalent to 375 mg naproxen.

Naprelan 500: white, capsule-shaped tablet with “N” on one side and “500” on the reverse; in bottles of 75; NDC 52427-273-75. Each tablet contains 550 mg naproxen sodium equivalent to 500 mg naproxen.

Naprelan 750:  white, capsule-shaped tablet with “N” on one side and “750” on the reverse; in bottles of 30; NDC 52427-274-30.  Each tablet contains 825 mg naproxen sodium equivalent to 750 mg naproxen.

Storage
Store at room temperature, 20° to 25° C (68° to 77° F), excursions permitted 15° to 30° C (59° to 86° F)[see USP Controlled Room Temperature].
PHARMACIST:  Dispense in a well-closed container.

Patient Counseling Information

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 Naprelan 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
Naprelan, like other NSAIDs, can cause GI discomfort and, rarely, serious GI side effects, such as ulcers and bleeding, which may result in hospitalization and even death. 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 Naprelan 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
Naprelan, like other NSAIDs, can cause serious skin side effects such as exfoliative dermatitis, SJS, and TEN, which may result in hospitalization and even death.  Advise patients to stop Naprelan 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 Naprelan, 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 Naprelan 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 Naprelan 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 Naprelan until they talk to their healthcare provider [see Drug Interactions (7)].

All trademarks are the property of their respective owners.

To request medical information or to report SUSPECTED ADVERSE REACTIONS, contact Almatica at 1-877-447-7979 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Product of Italy

Distributed by: Almatica Pharma, Inc.
Pine Brook, NJ 07058 USA

PI272-05

Medication Guide for Nonsteroidal Anti-inflammatory Drugs (NSAIDs)
What is the most important information I should know about medicines called Nonsteroidal Anti-inflammatory Drugs (NSAIDs)?

NSAIDs can cause serious side effects, including:
  • Increased risk of a heart attack or stroke that can lead to death. This risk may happen early in treatment and may increase:
    • 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 stomach 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 get any of the following symptoms:
  • shortness of breath or trouble breathing
  • chest pain
  • weakness in one part or side of your body
  • slurred speech
  • swelling of the face or throat
Stop taking your NSAID and call your healthcare provider right away if you get any of the following symptoms:
  • nausea
  • more tired or weaker than usual
  • diarrhea
  • itching
  • your skin or eyes look yellow
  • indigestion or stomach pain
  • flu-like symptoms
  • vomit blood
  • there is blood in your bowel movement or it is black and sticky like tar
  • unusual weight gain
  • skin rash or blisters with fever
  • swelling of the arms, legs, hands and feet
If you take too much of your NSAID, call your healthcare provider or get medical help right away.
These are not all the possible side effects of NSAIDs. For more information, ask your healthcare provider or pharmacist about NSAIDs.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Other information about NSAIDs
  • Aspirin is an NSAID but it does not increase the chance of a heart attack. Aspirin can cause bleeding in the brain, stomach, and intestines. Aspirin can also cause ulcers in the stomach and intestines.
  • Some NSAIDs are sold in lower doses without a prescription (over-the counter). Talk to your healthcare provider before using over-the-counter NSAIDs for more than 10 days.
General information about the safe and effective use of NSAIDs
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use NSAIDs for a condition for which it was not prescribed. Do not give NSAIDs to other people, even if they have the same symptoms that you have. It may harm them. If you would like more information about NSAIDs, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about NSAIDs that is written for health professionals.
Product of Italy
Distributed by: Almatica Pharma, Inc., Pine Brook, NJ 07058 USA For more information, call 1-877-447-7979

This Medication Guide has been approved by the U.S. Food and Drug Administration.
PL272-05
Rev. 09/2017

NDC 52427-272-01 Rx Only

375 mg
Naprelan®
(naproxen sodium)
CONTROLLED-RELEASE TABLETS

Each tablet contains 412.5 mg naproxen
sodium equivalent to 375 mg naproxen


100 Tablets
Almatica®

NDC 52427-273-75 Rx Only

500 mg
Naprelan®
(naproxen sodium)
CONTROLLED-RELEASE TABLETS

Each tablet contains 550 mg naproxen
sodium equivalent to 500 mg naproxen


75 Tablets
Almatica®

NDC 52427-274-30 Rx Only

750 mg
Naprelan®
(naproxen sodium)
CONTROLLED-RELEASE TABLETS

Each tablet contains 825 mg naproxen
sodium equivalent to 750 mg naproxen


30 Tablets
Almatica®

Naprelan 
naproxen sodium tablet, film coated, extended release
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:52427-272
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
NAPROXEN SODIUM (NAPROXEN) NAPROXEN 375 mg
Inactive Ingredients
Ingredient Name Strength
AMMONIO METHACRYLATE COPOLYMER TYPE A  
AMMONIO METHACRYLATE COPOLYMER TYPE B  
CITRIC ACID MONOHYDRATE  
CROSPOVIDONE  
MAGNESIUM STEARATE  
METHACRYLIC ACID - METHYL METHACRYLATE COPOLYMER (1:1)  
CELLULOSE, MICROCRYSTALLINE  
POVIDONE  
TALC  
HYPROMELLOSES  
POLYETHYLENE GLYCOLS  
TITANIUM DIOXIDE  
Product Characteristics
Color WHITE Score no score
Shape CAPSULE Size 15mm
Flavor Imprint Code N;375
Contains     
Packaging
# Item Code Package Description
1 NDC:52427-272-01 100 TABLET, FILM COATED, EXTENDED RELEASE in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA020353 01/17/2014
Naprelan 
naproxen sodium tablet, film coated, extended release
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:52427-273
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
NAPROXEN SODIUM (NAPROXEN) NAPROXEN 500 mg
Inactive Ingredients
Ingredient Name Strength
AMMONIO METHACRYLATE COPOLYMER TYPE A  
AMMONIO METHACRYLATE COPOLYMER TYPE B  
CITRIC ACID MONOHYDRATE  
CROSPOVIDONE  
MAGNESIUM STEARATE  
METHACRYLIC ACID - METHYL METHACRYLATE COPOLYMER (1:1)  
CELLULOSE, MICROCRYSTALLINE  
POVIDONE  
TALC  
HYPROMELLOSES  
POLYETHYLENE GLYCOLS  
TITANIUM DIOXIDE  
Product Characteristics
Color WHITE Score no score
Shape CAPSULE Size 17mm
Flavor Imprint Code N;500
Contains     
Packaging
# Item Code Package Description
1 NDC:52427-273-75 75 TABLET, FILM COATED, EXTENDED RELEASE in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA020353 01/17/2014
Naprelan 
naproxen sodium tablet, film coated, extended release
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:52427-274
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
NAPROXEN SODIUM (NAPROXEN) NAPROXEN 750 mg
Inactive Ingredients
Ingredient Name Strength
AMMONIO METHACRYLATE COPOLYMER TYPE A  
AMMONIO METHACRYLATE COPOLYMER TYPE B  
CITRIC ACID MONOHYDRATE  
CROSPOVIDONE  
MAGNESIUM STEARATE  
METHACRYLIC ACID - METHYL METHACRYLATE COPOLYMER (1:1)  
CELLULOSE, MICROCRYSTALLINE  
POVIDONE  
TALC  
HYPROMELLOSES  
POLYETHYLENE GLYCOLS  
TITANIUM DIOXIDE  
Product Characteristics
Color WHITE Score no score
Shape CAPSULE Size 22mm
Flavor Imprint Code N;750
Contains     
Packaging
# Item Code Package Description
1 NDC:52427-274-30 30 TABLET, FILM COATED, EXTENDED RELEASE in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA020353 01/17/2014
Labeler - ALMATICA PHARMA INC. (962454505)
Establishment
Name Address ID/FEI Operations
NORWICH PHARMACEUTICALS, INC. 132218731 pack(52427-272, 52427-273, 52427-274), manufacture(52427-272, 52427-273, 52427-274)
Revised: 09/2017   ALMATICA PHARMA INC.
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