Nudroxipak

Name: Nudroxipak

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 the treatment and may increase with duration of use [see Warnings and Precautions (5.1)].
  • Celecoxib is 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)]

Indications and usage

Osteoarthritis

For the management of the signs and symptoms of OA [ see Clinical Studies (14.1)]

Rheumatoid Arthritis

For the management of the signs and symptoms of RA [ see Clinical Studies (14.2)]

Juvenile Rheumatoid Arthritis

For the management of the signs and symptoms of JRA in patients 2 years and older [ see Clinical Studies (14.3)]

Ankylosing Spondylitis

For the management of the signs and symptoms of AS [ see Clinical Studies (14.4)]

Acute Pain

For the management of acute pain in adults [ see Clinical Studies (14.5)]

Primary Dysmenorrhea

For the management of primary dysmenorrhea [ see Clinical Studies (14.5)]

Dosage Forms and Strengths

Capsules: 50 mg, 100 mg and 200 mg

Drug Interactions

See Table 3 for clinically significant drug interactions with celecoxib.

Table 3: Clinically Significant Drug Interactions with Celecoxib

Drugs That Interfere with Hemostasis
  Clinical Impact: Celecoxib and anticoagulants such as warfarin have a synergistic effect on bleeding. The concomitant use of celecoxib and anticoagulants have an increased risk of serious bleeding compared to the use of either drug alone. Serotonin release by platelets plays an important role in hemostasis. Case-control and cohort epidemiological studies showed that concomitant use of drugs that interfere with serotonin reuptake and an NSAID may potentiate the risk of bleeding more than an NSAID alone.
Intervention: Monitor patients with concomitant use of celecoxib capsules 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)]. In two studies in healthy volunteers, and in patients with osteoarthritis and established heart disease respectively, celecoxib (200-400 mg daily) has demonstrated a lack of interference with the cardioprotective antiplatelet effect of aspirin (100-325 mg).
Intervention: Concomitant use of celecoxib capsules and analgesic doses of aspirin is not generally recommended because of the increased risk of bleeding [ see Warnings and Precautions (5.11)]. Celecoxib capsules 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 celecoxib capsules and ACE-inhibitors, ARBs, or beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained.
  • During concomitant use of celecoxib capsules 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 celecoxib capsules 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 celecoxib with digoxin has been reported to increase the serum concentration and prolong the half-life of digoxin.
Intervention: During concomitant use of celecoxib capsules 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 celecoxib capsules 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).
Celecoxib capsules have no effect on methotrexate pharmacokinetics.
Intervention: During concomitant use of celecoxib capsules and methotrexate, monitor patients for methotrexate toxicity.
Cyclosporine
Clinical Impact: Concomitant use of celecoxib capsules and cyclosporine may increase cyclosporine’s nephrotoxicity.
Intervention: During concomitant use of celecoxib capsules and cyclosporine, monitor patients for signs of worsening renal function.
NSAIDs and Salicylates
Clinical Impact: Concomitant use of celecoxib 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 celecoxib with other NSAIDs or salicylates is not recommended.
Pemetrexed
Clinical Impact: Concomitant use of celecoxib capsules and pemetrexed may increase the risk of pemetrexed-associated myelosuppression, renal, and GI toxicity (see the pemetrexed prescribing information).
Intervention: During concomitant use of celecoxib capsules 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.
CYP2C9 Inhibitors or inducers
Clinical Impact: Celecoxib metabolism is predominantly mediated via cytochrome P450 (CYP) 2C9 in the liver. Co­-administration of celecoxib with drugs that are known to inhibit CYP2C9 (e.g. fluconazole) may enhance the exposure and toxicity of celecoxib whereas co-administration with CYP2C9 inducers (e.g. rifampin) may lead to compromised efficacy of celecoxib.
Intervention Evaluate each patient's medical history when consideration is given to prescribing celecoxib. A dosage adjustment may be warranted when celecoxib is administered with CYP2C9 inhibitors or inducers [ see Clinical Pharmacology (12.3)].
CYP2D6 substrates
Clinical Impact: In vitro studies indicate that celecoxib, although not a substrate, is an inhibitor of CYP2D6. Therefore, there is a potential for an in vivo drug interaction with drugs that are metabolized by CYP2D6 (e.g. atomoxetine), and celecoxib may enhance the exposure and toxicity of these drugs.
Intervention Evaluate each patient's medical history when consideration is given to prescribing celecoxib. A dosage adjustment may be warranted when celecoxib is administered with CYP2D6 substrates [ see Clinical Pharmacology (12.3)].
Corticosteroids
Clinical Impact: Concomitant use of corticosteroids with celecoxib capsules may increase the risk of GI ulceration or bleeding.
Intervention Monitor patients with concomitant use of celecoxib capsules with corticosteroids for signs of bleeding [see Warnings and Precautions (5.2)].

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis
Celecoxib was not carcinogenic Sprague-Dawley in rats given oral doses up to 200 mg/kg for males and 10 mg/kg for females (approximately 2-to 4-times the human exposure as measured by the AUC 0-24 at 200 mg twice daily) or in mice given oral doses up to 25 mg/kg for males and 50 mg/kg for females (approximately equal to human exposure as measured by the AUC 0-24 at 200 mg twice daily) for two years.

Mutagenesis
Celecoxib was not mutagenic in an Ames test and a mutation assay in Chinese hamster ovary (CHO) cells, nor clastogenic in a chromosome aberration assay in CHO cells and an in vivo micronucleus test in rat bone marrow.

Impairment of Fertility
Celecoxib had no effect on male or female fertility or male reproductive function in rats at oral doses up to 600 mg/kg/day (approximately 11 times human exposure at 200 mg twice daily based on the AUC 0-24). At ≥50 mg/kg/day (approximately 6-times human exposure based on the AUC 0-24 at 200 mg twice daily) there was increased preimplantation loss.

Animal Toxicology

An increase in the incidence of background findings of spermatocele with or without secondary changes such as epididymal hypospermia as well as minimal to slight dilation of the seminiferous tubules was seen in the juvenile rat. These reproductive findings while apparently treatment-related did not increase in incidence or severity with dose and may indicate an exacerbation of a spontaneous condition. Similar reproductive findings were not observed in studies of juvenile or adult dogs or in adult rats treated with celecoxib. The clinical significance of this observation is unknown.

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 celecoxib capsules 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 celecoxib capsules and seek immediate medical therapy [ see Warnings and Precautions (5.3), Use in Specific Populations (8.6)].

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 celecoxib capsules 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 celecoxib capsules, 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 celecoxib capsules and other NSAIDs starting at 30 weeks of 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 celecoxib capsules 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 celecoxib capsules until they talk to their healthcare provider [see Drug Interactions (7)].

APOTEX INC.
CELECOXIB CAPSULES
50 mg, 100 mg and 200 mg

Manufactured by:
Apotex Inc.
Toronto, Ontario
Canada M9LIT9
Manufactured by:
Apotex Research Pvt. Ltd.
Bangalore - 560 099
India
Manufactured for:
Apotex Corp.
Weston, Florida
33326

Revised: November 2016

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.

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

Manufactured by
Apotex Inc
Toronto, Ontario
Canada M9L 1T9
Manufactured by
Apotex Research Pvt. Ltd.
Bangalore - 560 099
Manufactured for
Apotex Corp.
Weston, Florida
USA 33326

Revised: November 2016

Do not use

On cuts or infected skin, on children less than 12 years old in large amount.

Nudroxipak pain relief PAK

Nudroxipak 
celecoxib,methyl salicylate/menthol/capsaicin kit
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:70859-029
Packaging
# Item Code Package Description
1 NDC:70859-029-01 1 KIT in 1 CARTON
Quantity of Parts
Part # Package Quantity Total Product Quantity
Part 1 1 BOTTLE 100 
Part 2 1 CONTAINER 90 mL
Part 1 of 2
CELECOXIB 
celecoxib capsule
Product Information
Item Code (Source) NDC:60505-3849
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
CELECOXIB (CELECOXIB) CELECOXIB 200 mg
Inactive Ingredients
Ingredient Name Strength
DIMETHICONE  
POVIDONE  
BUTYL ALCOHOL  
TITANIUM DIOXIDE  
SHELLAC  
ALCOHOL  
ISOPROPYL ALCOHOL  
PROPYLENE GLYCOL  
FERRIC OXIDE YELLOW  
CROSPOVIDONE (15 MPA.S AT 5%)  
AMMONIA  
SODIUM LAURYL SULFATE  
MAGNESIUM STEARATE  
GELATIN  
Product Characteristics
Color white Score no score
Shape CAPSULE Size 18mm
Flavor Imprint Code APO;C200
Contains     
Packaging
# Item Code Package Description
1 NDC:60505-3849-1 100 CAPSULE in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA204197 06/03/2015
Part 2 of 2
NUDROXICIN PAIN RELIEF ROLL-ON 
methyl salicylate, menthol, capsaicin liquid
Product Information
Item Code (Source) NDC:70859-028
Route of Administration TOPICAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
CAPSAICIN (CAPSAICIN) CAPSAICIN 0.25 mg  in 1 mL
METHYL SALICYLATE (SALICYLIC ACID) METHYL SALICYLATE 250 mg  in 1 mL
MENTHOL (MENTHOL) MENTHOL 60 mg  in 1 mL
Inactive Ingredients
Ingredient Name Strength
YELLOW WAX  
CETEARYL OLIVATE  
POLYSORBATE 20  
ARNICA MONTANA FLOWER  
ETHYLHEXYLGLYCERIN  
ILEX PARAGUARIENSIS LEAF  
WATER  
SORBITAN OLIVATE  
PHENOXYETHANOL  
DIMETHYL SULFONE  
INDIAN FRANKINCENSE  
CARBOXYPOLYMETHYLENE  
MAGNESIUM SULFATE, UNSPECIFIED FORM  
GLYCERYL MONOSTEARATE  
Packaging
# Item Code Package Description
1 NDC:70859-028-03 1 CONTAINER in 1 CARTON
1 90 mL in 1 CONTAINER
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
OTC monograph not final part348 02/07/2018
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA204197 02/08/2018
Labeler - NuCare Pharmaceuticals,Inc. (010632300)
Establishment
Name Address ID/FEI Operations
NuCare Pharmaceuticals,Inc. 010632300 manufacture(70859-029)
Revised: 02/2018   NuCare Pharmaceuticals,Inc.
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