TEVA-PIROXICAM CAPSULE

Canada - English - Health Canada

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Active ingredient:
PIROXICAM
Available from:
TEVA CANADA LIMITED
ATC code:
M01AC01
INN (International Name):
PIROXICAM
Dosage:
10MG
Pharmaceutical form:
CAPSULE
Composition:
PIROXICAM 10MG
Administration route:
ORAL
Units in package:
100/250/500
Prescription type:
Prescription
Therapeutic area:
OTHER NONSTEROIDAL ANTIIMFLAMMATORY AGENTS
Product summary:
Active ingredient group (AIG) number: 0114612002; AHFS: 28:08.04.92
Authorization status:
APPROVED
Authorization number:
00695718
Authorization date:
2014-06-12

Documents in other languages

Page 1

PRODUCT MONOGRAPH

Pr

TEVA-PIROXICAM

Piroxicam

10 mg and 20 mg Capsules, USP

Nonsteroidal Anti-inflammatory Drug (NSAID)

Teva Canada Limited

30 Novopharm Court

Toronto, Ontario

M1B 2K9

www.tevacanada.com

Submission Control No: 184805

Date of Revision:

July 14, 2015

Page 2

Table of Contents

PART I: HEALTH PROFESSIONAL INFORMATION ......................................................... 3

SUMMARY PRODUCT INFORMATION ......................................................................... 3

INDICATIONS AND CLINICAL USE .............................................................................. 3

CONTRAINDICATIONS .................................................................................................... 4

WARNINGS AND PRECAUTIONS .................................................................................. 5

ADVERSE REACTIONS .................................................................................................. 14

DRUG INTERACTIONS .................................................................................................. 19

DOSAGE AND ADMINISTRATION .............................................................................. 22

OVERDOSAGE ................................................................................................................. 24

ACTION AND CLINICAL PHARMACOLOGY ............................................................. 24

STORAGE AND STABILITY .......................................................................................... 25

DOSAGE FORMS, COMPOSITION AND PACKAGING .............................................. 26

PART II: SCIENTIFIC INFORMATION ............................................................................... 27

PHARMACEUTICAL INFORMATION .......................................................................... 27

CLINICAL TRIALS .......................................................................................................... 28

DETAILED PHARMACOLOGY ..................................................................................... 28

TOXICOLOGY .................................................................................................................. 29

REFERENCES ................................................................................................................... 32

PART III: CONSUMER INFORMATION .............................................................................. 34

Page 3

Pr

TEVA-PIROXICAM

Piroxicam

PART I: HEALTH PROFESSIONAL INFORMATION

SUMMARY PRODUCT INFORMATION

Route of

Administration

Dosage Form / Strength

Clinically Relevant Nonmedicinal

Ingredients

Oral

Capsules, 10 mg and 20 mg

None

For a complete listing see Dosage Forms,

Composition and Packaging section.

INDICATIONS AND CLINICAL USE

TEVA-PIROXICAM (piroxicam) is indicated for the symptomatic treatment of:

rheumatoid arthritis,

osteoarthritis (degenerative joint disease) and

ankylosing spondylitis.

Throughout this document, the term NSAIDs refers to both non-selective NSAIDs and selective

COX-2 inhibitor NSAIDs, unless otherwise indicated.

For patients with an increased risk of developing CV and/or GI adverse events, other

management strategies that do NOT include the use of NSAIDs should be considered first.

(See Contraindications and Warnings and Precautions)

Use of TEVA-PIROXICAM should be limited to the lowest effective dose for the shortest

possible duration of treatment in order to minimize the potential risk for cardiovascular or

gastrointestinal adverse events. (See Contraindications and Warnings and Precautions)

TEVA-PIROXICAM, as a NSAID, does NOT treat clinical disease or prevent its progression.

TEVA-PIROXICAM, as a NSAID, only relieves symptoms and decreases inflammation for as

long as the patient continues to take it.

Page 4

Geriatrics(> 65 years of age): Evidence from clinical studies and postmarket experience

suggests that use in the geriatric population is associated with differences in safety (See

Warnings and Precautions).

Pediatrics(< 16 years of age): Safety and efficacy have not been established in the pediatric

population.

CONTRAINDICATIONS

TEVA-PIROXICAM is contraindicated in:

the peri-operative setting of coronary artery bypass graft surgery (CABG). Although

TEVA-PIROXICAM has NOT been studied in this patient population, a selective COX-2

inhibitor NSAID studied in such a setting has led to an increased incidence of

cardiovascular/thromboembolic events, deep surgical infections and sternal wound

complications.

the third trimester of pregnancy, because of risk of premature closure of the ductus

arteriosus and prolonged parturition

women who are breastfeeding, because of the potential for serious adverse reactions in

nursing infants

severe uncontrolled heart failure

known hypersensitivity to piroxicam or to any of the components/excipients of TEVA-

PIROXICAM.

history of asthma, urticaria, or allergic-type reactions after taking acetylsalicylic acid

(ASA) or other NSAIDs (i.e. complete or partial syndrome of ASA-intolerance -

rhinosinusitis, urticaria/ angioedema, nasal polyps, asthma). Fatal anaphylactoid

reactions have occurred in such individuals. Individuals with the above medical problems

are at risk of a severe reaction even if they have taken NSAIDs in the past without any

adverse reaction. The potential for cross-reactivity between different NSAIDs must be

kept in mind (see Warnings and Precautions Hypersensitivity Reactions -

Anaphylactoid Reactions).

active gastric / duodenal / peptic ulcer or active inflammatory disease of the

gastrointestinal system, active GI bleeding or patients with a recent or recurrent history of

these conditions.

cerebrovascular bleeding or other bleeding disorders

inflammatory bowel disease

Page 5

severe liver impairment or active liver disease

severe renal impairment (creatinine clearance <30 mL/min or 0.5 mL/sec) or

deteriorating renal disease (individuals with lesser degrees of renal impairment are at risk

of deterioration of their renal function when prescribed NSAIDs and must be monitored)

(see Warnings and Precautions - Renal)

known hyperkalemia (see Warnings and Precautions - Renal - Fluid and Electrolyte

Balance)

children and adolescents less than 16 years of age

WARNINGS AND PRECAUTIONS

Risk of Cardiovascular (CV) Adverse Events: Ischemic Heart Disease,

Cerebrovascular Disease, Congestive Heart Failure (NYHA II-IV)

(See Warnings and Precautions - Cardiovascular).

TEVA-PIROXICAM is a non-steroidal anti-inflammatory drug (NSAID). Use of some

NSAIDs is associated with an increased incidence of cardiovascular adverse events (such as

myocardial infarction, stroke or thrombotic events) which can be fatal. The risk may

increase with duration of use. Patients with cardiovascular disease or risk factors for

cardiovascular disease may be at greater risk.

Caution should be exercised in prescribing TEVA-PIROXICAM to any patient with

ischemic heart disease (including but NOT limited to acute myocardial infarction, history of

myocardial infarction and/or angina), cerebrovascular disease (including but NOT limited

to stroke, cerebrovascular accident, transient ischemic attacks and/or amaurosis fugax)

and/or congestive heart failure (NYHA II-IV).

Use of TEVA-PIROXICAM, can promote sodium retention in a dose-dependent manner,

through a renal mechanism, which can result in increased blood pressure and/or

exacerbation of congestive heart failure. (see also Warnings and Precautions - Renal - Fluid

and Electrolyte Balance)

Randomized clinical trials with TEVA-PIROXICAM have not been designed to detect

differences in cardiovascular events in a chronic setting. Therefore, caution should be

exercised when prescribing TEVA-PIROXICAM.

Risk of Gastrointestinal (GI) Adverse Events

(see Warnings and Precautions

Gastrointestinal).

Page 6

Use of TEVA-PIROXICAM, is associated with an increased incidence of gastrointestinal

adverse events (such as peptic/duodenal ulceration, perforation, obstruction and

gastrointestinal bleeding).

General

Frail or debilitated patients may tolerate side effects less well and therefore special care should be

taken in treating this population. To minimize the potential risk for an adverse event, the

lowest effective dose should be used for the shortest possible duration. As with other

NSAIDs, caution should be used in the treatment of elderly patients who are more likely to be

suffering from impaired renal, hepatic or cardiac function. For high risk patients, alternate

therapies that do not involve NSAIDs should be considered.

TEVA-PIROXICAM is NOT recommended for use with other NSAIDs, with the exception of

low-dose ASA for cardiovascular prophylaxis, because of the absence of any evidence

demonstrating synergistic benefits and the potential for additive adverse reactions. (See Drug

Interactions - Drug/Drug Interactions - Acetylsalicylic acid (ASA) or other NSAIDs)

Carcinogenesis and Mutagenesis

(see Toxicology Section)

Cardiovascular

TEVA-PIROXICAM is a non-steroidal anti-inflammatory drug (NSAID). Use of some

NSAIDs is associated with an increased incidence of cardiovascular adverse events (such as

myocardial infarction, stroke or thrombotic events) which can be fatal. The risk may

increase with duration of use. Patients with cardiovascular disease or risk factors for

cardiovascular disease may be at greater risk.

Caution should be exercised in prescribing TEVA-PIROXICAM to patients with risk

factors for cardiovascular disease, cerebrovascular disease or renal disease, such as any of

the following (NOT an exhaustive list)

Hypertension

Dyslipidemia / Hyperlipidemia

Diabetes Mellitus

Congestive Heart Failure (NYHA I)

Coronary Artery Disease (Atherosclerosis)

Peripheral Arterial Disease

Smoking

Creatinine Clearance < 60 mL/min or 1 mL/sec

Use of NSAIDs, such as TEVA-PIROXICAM, can lead to new hypertension or can worsen pre-

existing hypertension, either of which may increase the risk of cardiovascular events as described

Page 7

above. Thus blood pressure should be monitored regularly. Consideration should be given to

discontinuing TEVA-PIROXICAM should hypertension either develop or worsen with its use.

Use of NSAIDs, such as TEVA-PIROXICAM, can induce fluid retention and edema, and may

exacerbate congestive heart failure, through a renally-mediated mechanism. (See Warnings and

Precautions - Renal - Fluid and Electrolyte Balance).

For patients with a high risk of developing an adverse CV event, other management strategies

that do NOT include the use of NSAIDs should be considered first. To minimize the potential

risk for an adverse CV event, the lowest effective dose should be used for the shortest

possible duration.

Endocrine and Metabolism

Corticosteroids:

TEVA-PIROXICAM (piroxicam) is NOT a substitute for corticosteroids. It does NOT treat

corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to exacerbation

of corticosteroid-responsive illness. Patients on prolonged corticosteroid therapy should have

their therapy tapered slowly if a decision is made to discontinue corticosteroids. (see Drug

Interactions - Drug-Drug Interactions - Glucocorticoids)

Gastrointestinal (GI)

Serious GI toxicity (sometimes fatal), such as peptic / duodenal ulceration, inflammation,

perforation, obstruction and gastrointestinal bleeding, can occur at any time, with or without

warning symptoms, in patients treated with NSAIDs, including TEVA-PIROXICAM. Minor

upper GI problems, such as dyspepsia, commonly occur at any time. Health care providers should

remain alert for ulceration and bleeding in patients treated with TEVA-PIROXICAM, even in the

absence of previous GI tract symptoms. Most spontaneous reports of fatal GI events are in elderly

or debilitated patients and therefore special care should be taken in treating this population. To

minimize the potential risk for an adverse GI event, the lowest effective dose should be used

for the shortest possible duration. For high risk patients, alternate therapies that do not involve

NSAIDs should be considered. (see Warnings and Precautions - Special Populations -

Geriatrics)

Evidence from epidemiological studies suggests that piroxicam is associated with a high risk of

gastrointestinal toxicity relative to some other NSAIDs.

Patients should be informed about the signs and/or symptoms of serious GI toxicity and

instructed to discontinue using TEVA-PIROXICAM and seek emergency medical attention if

they experience any such symptoms. The utility of periodic laboratory monitoring has NOT been

demonstrated, nor has it been adequately assessed. Most patients who develop a serious upper GI

adverse event on NSAID therapy have no symptoms. Upper GI ulcers, gross bleeding or

perforation, caused by NSAIDs, appear to occur in approximately 1% of patients treated for 3-6

months, and in about 2-4% of patients treated for one year. These trends continue, thus increasing

the likelihood of developing a serious GI event at some time during the course of therapy. Even

short-term therapy has its risks.

Page 8

Caution should be taken if prescribing TEVA-PIROXICAM to patients with a prior history of

peptic / duodenal ulcer disease or gastrointestinal bleeding as these individuals have a greater

than 10-fold higher risk for developing a GI bleed when taking a NSAID than patients with

neither of these risk factors. Other risk factors for GI ulceration and bleeding include the

following: Helicobacter pylori infection, increased age, prolonged use of NSAID therapy, excess

alcohol intake, smoking, poor general health status or concomitant therapy with any of the

following:

Anti-coagulants (e.g. warfarin)

Anti-platelet agents (e.g. ASA, clopidogrel)

Oral corticosteroids (e.g. prednisone)

Selective Serotonin Reuptake Inhibitors (SSRIs) (e.g. citalopram, fluoxetine, paroxetine,

sertraline)

Gastrointestinal side effects are dose-related and doses of piroxicam greater than 20 mg daily

should not be used. The minimum maintenance dose needed to control symptoms is

recommended.

Genitourinary

Some NSAIDs are associated with persistent urinary symptoms (bladder pain, dysuria, urinary

frequency), hematuria or cystitis. The onset of these symptoms may occur at any time after the

initiation of therapy with an NSAID. Should urinary symptoms occur, in the absence of an

alternate explanation, treatment with TEVA-PIROXICAM should be stopped to ascertain if

symptoms disappear. This should be done before urological investigations or treatments are

carried out.

Hematologic

NSAIDs inhibiting prostaglandin biosynthesis interfere with platelet function to varying degrees;

patients who may be adversely affected by such an action, such as those on anti-coagulants or

suffering from haemophilia or platelet disorders should be carefully observed when TEVA-

PIROXICAM is administered.

Anti-coagulants:

Piroxicam is highly protein-bound, and therefore, might be expected to displace other protein-

bound drugs. The physician should closely monitor dosage requirements of coumarin

anticoagulants and other drugs that are highly protein-bound when these are administered

concomitantly with piroxicam.

Numerous studies have shown that the concomitant use of NSAIDs and anti-coagulants increases

the risk of bleeding. Concurrent therapy of TEVA-PIROXICAM with warfarin requires close

monitoring of the international normalized ratio (INR). Even with therapeutic INR monitoring,

increased bleeding may occur.

Anti-platelet Effects:

Page 9

NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some

patients. Unlike acetylsalicylic acid (ASA), their effect on platelet function is quantitatively less,

or of shorter duration, and is reversible.

TEVA-PIROXICAM and other NSAIDs have no proven efficacy as anti-platelet agents and

should NOT be used as a substitute for ASA or other anti-platelet agents for prophylaxis of

cardiovascular thromboembolic diseases. Anti-platelet therapies (e.g. ASA) should NOT be

discontinued. There is some evidence that use of NSAIDs with ASA can markedly attenuate the

cardioprotective effects of ASA. (see Drug Interactions - Drug-Drug Interactions -

Acetylsalicylic Acid (ASA) or other NSAIDs)

Concomitant administration of TEVA-PIROXICAM with low dose ASA increases the risk of GI

ulceration and associated complications.

Blood dyscrasias:

Blood dyscrasias (such as neutropenia, leukopenia, thrombocytopenia, aplastic anemia and

agranulocytosis) associated with the use of NSAIDs are rare, but could occur with severe

consequences.

Anemia is sometimes seen in patients receiving NSAIDs, including TEVA-PIROXICAM. This

may be due to fluid retention, GI blood loss, or an incompletely described effect upon

erythropoiesis. In clinical trials with piroxicam hematologic adverse reactions occurred

very commonly (15%) (See Adverse Reactions – Clinical Trial Adverse Drug Reactions

Hematologic). At the recommended dose of 20 mg/day of piroxicam, reductions in hemoglobin

and hematocrit values are observed in about 4% of the patients treated with piroxicam alone or

concomitantly with ASA. These observations occurred in the absence of fecal blood loss due to

gastrointestinal irritation. Therefore, hematocrit and hemoglobin values should be determined

periodically.

Hepatic/Biliary/Pancreatic

As with other NSAIDs, borderline elevations of one or more liver enzyme tests (AST, ALT,

alkaline phosphatase) may occur in up to 15% of patients. These abnormalities may progress,

may remain essentially unchanged, or may be transient with continued therapy. Elevations of

ALT and AST 3 times the upper limit of normal, occurred in controlled clinical trials in less than

1% of patients. Hepatitis and jaundice occurred in less than 1% of patients.

A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal

liver function test has occurred, should be evaluated for evidence of the development of a more

severe hepatic reaction while on therapy with this drug. Severe hepatic reactions including

jaundice and cases of fatal hepatitis, liver necrosis and hepatic failure, some of them with fatal

outcomes, have been reported with piroxicam.

Although such reactions are rare, if abnormal liver tests persist or worsen, if clinical signs and

symptoms consistent with liver disease develop (e.g. jaundice), or if systemic manifestations

occur (e.g. eosinophilia, associated with rash, etc.), this drug should be discontinued.

Page 10

If there is a need to prescribe this drug in the presence of impaired liver function, it must be done

under strict observation.

Hypersensitivity Reactions

Anaphylactoid Reactions:

As with NSAIDs in general, anaphylactoid reactions have occurred in patients without known

prior exposure to TEVA-PIROXICAM. In post-marketing experience, rare cases of anaphylactic/

anaphylactoid reactions and angioedema have been reported in patients receiving TEVA-

PIROXICAM. TEVA-PIROXICAM should NOT be given to patients with the ASA-triad. This

symptom complex typically occurs in asthmatic patients who experience rhinitis with or without

nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking ASA or other

NSAIDs (see Contraindications).

ASA-Intolerance:

TEVA-PIROXICAM should NOT be given to patients with complete or partial syndrome of

ASA-intolerance (rhinosinusitis, urticaria/angioedema, nasal polyps, asthma) in whom asthma,

anaphylaxis, urticaria/angioedema, rhinitis or other allergic manifestations are precipitated by

ASA or other NSAIDs. Fatal anaphylactoid reactions have occurred in such individuals. As well,

individuals with the above medical problems are at risk of a severe reaction even if they have

taken NSAIDs in the past without any adverse reaction (see Contraindications).

Cross-sensitivity:

Patients sensitive to one NSAID may be sensitive to any of the other NSAIDs as well.

Serious skin reactions:

(See Warnings and Precautions - Skin)

Evidence from epidemiological studies suggests that piroxicam is associated with a higher risk of

serious skin reactions compared to other non-oxicam NSAIDS.

Immune

(See Warnings and Precautions - Infection- Aseptic Meningitis)

Infection

TEVA-PIROXICAM, in common with other NSAIDs, may mask signs and symptoms of an

underlying infectious disease.

Aseptic Meningitis:

Rarely, with some NSAIDs, including TEVA-PIROXICAM, the symptoms of aseptic meningitis

(stiff neck, severe headaches, nausea and vomiting, fever or clouding of consciousness) have

been observed. Patients with autoimmune disorders (systemic lupus erythematosus, mixed

connective tissue diseases, etc.) seem to be pre-disposed. Therefore, in such patients, the health

care provider must be vigilant to the development of this complication.

Page 11

Neurologic

Some patients may experience drowsiness, dizziness, blurred vision, vertigo, tinnitus, hearing

loss, insomnia or depression with the use of NSAIDs, such as TEVA-PIROXICAM. If patients

experience such adverse reaction(s), they should exercise caution in carrying out activities that

require alertness.

Ophthalmologic

Blurred and/or diminished vision has been reported with the use of piroxicam and other NSAIDs.

If such symptoms develop TEVA-PIROXICAM should be discontinued and an ophthalmologic

examination performed. Ophthalmologic examination should be carried out at periodic intervals

in any patient receiving TEVA-PIROXICAM for an extended period of time.

Peri-Operative Considerations

(See Contraindications - Coronary Artery Bypass Graft Surgery)

Psychiatric

(See Warnings and Precautions – Neurologic)

Renal

Long term administration of piroxicam to animals has resulted in renal papillary necrosis and

other abnormal renal pathology. In humans, there have been reports of acute interstitial nephritis,

hematuria, proteinuria and occasionally nephrotic syndrome.

Acute renal failure and hyperkalemia as well as reversible elevations of BUN and serum

creatinine have been reported with piroxicam.

Renal insufficiency due to NSAID use is seen in patients with pre-renal conditions leading to

reduction in renal blood flow or blood volume. Under these circumstances, renal prostaglandins

help maintain renal perfusion and glomerular filtration rate (GFR). In these patients,

administration of a NSAID may cause a reduction in prostaglandin synthesis leading to impaired

renal function. Patients at greatest risk of this reaction are those with pre-existing renal

insufficiency (GFR < 60 mL/min or 1 mL/s), dehydrated patients, patients on salt restricted diets,

those with congestive heart failure, cirrhosis, liver dysfunction, taking angiotensin-converting

enzyme inhibitors, angiotensin-II receptor blockers, cyclosporin, diuretics, and those who are

elderly. Serious or life-threatening renal failure has been reported in patients with normal or

impaired renal function after short term therapy with NSAIDs. Even patients at risk who

demonstrate the ability to tolerate a NSAID under stable conditions may decompensate during

periods of added stress (e.g. dehydration due to gastroenteritis). Discontinuation of NSAIDs is

usually followed by recovery to the pre-treatment state.

Caution should be used when initiating treatment with TEVA-PIROXICAM in patients with

considerable dehydration. Such patients should be rehydrated prior to initiation of therapy.

Caution is also recommended in patients with pre-existing kidney disease. Because of the

extensive renal excretion of TEVA-PIROXICAM and its biotransformation products (less than

5% of the daily dose excreted unchanged), lower doses of TEVA-PIROXICAM should be

anticipated in patients with impaired renal function and they should be carefully monitored.

Page 12

Advanced Renal Disease:

(See Contraindications)

Fluid and Electrolyte Balance:

Use of NSAIDs, including TEVA-PIROXICAM, can promote sodium retention in a dose-

dependent manner, which can lead to fluid retention and edema, and consequences of increased

blood pressure and exacerbation of congestive heart failure. Thus, caution should be exercised in

prescribing TEVA-PIROXICAM in patients with a history of congestive heart failure,

compromised cardiac function, hypertension, increased age or other conditions predisposing to

fluid retention (See Warnings and Precautions - Cardiovascular).

Use of NSAIDs, including TEVA-PIROXICAM, can increase the risk of hyperkalemia,

especially in patients with diabetes mellitus, renal failure, increased age, or those receiving

concomitant therapy with adrenergic blockers, angiotensin-converting enzyme inhibitors,

angiotensin-II receptor antagonists, cyclosporin, or some diuretics.

Electrolytes should be monitored periodically (see Contraindications).

Respiratory

ASA-induced asthma is an uncommon but very important indication of ASA and NSAID

sensitivity. It occurs more frequently in patients with asthma who have nasal polyps.

Sexual Function/Reproduction

The use of TEVA-PIROXICAM, as with any drug known to inhibit

cyclooxygenase/prostaglandin synthesis, may impair fertility and is not recommended in women

attempting to conceive. Therefore, in women who have difficulties conceiving, or who are

undergoing investigation of infertility, withdrawal of TEVA-PIROXICAM should be considered.

A combination of dermatological and/or allergic signs and symptoms suggestive of serum

sickness has occasionally occurred in conjunction with the use of piroxicam. These include

arthralgias, pruritus, fever, fatigue, and rash including vesiculo bullous reactions and exfoliative

dermatitis.

Skin

In rare cases, serious skin reactions such as Stevens-Johnson syndrome, toxic epidermal

necrolysis, exfoliative dermatitis and erythema multiforme have been associated with the use of

some NSAIDs, including TEVA-PIROXICAM. Because the rate of these reactions is low, they

have usually been noted during post-marketing surveillance in patients taking other medications

also associated with the potential development of these serious skin reactions. Thus, causality is

not clear. These reactions are potentially life threatening but may be reversible if the causative

agent is discontinued and appropriate treatment instituted. Patients should be advised that if they

experience a skin rash they should discontinue their NSAID and contact their physician for

assessment and advice, including which additional therapies to discontinue.

Page 13

Evidence from epidemiological studies suggests that piroxicam is associated with a higher risk of

serious skin reactions compared to other non-oxicam NSAIDs.

Photosensitivity has been occasionally associated with the use of piroxicam.

A combination of dermatological and/or allergic signs and symptoms suggestive of serum

sickness has occasionally occurred in conjunction with the use of piroxicam. These include

arthralgias, pruritus, fever, fatigue, and rash including vesiculo bullous reactions and exfoliative

dermatitis.

Special Populations

Pregnant Women:

TEVA-PIROXICAM is CONTRAINDICATED for use during the third trimester of

pregnancy because of risk of premature closure of the ductus arteriosus and the potential to

prolong parturition (see Toxicology).

The use of TEVA-PIROXICAM during the first and second trimester of pregnancy is not

recommended as its safety in this condition has not been established. Based on animal data

caution should be exercised in prescribing TEVA-PIROXICAM during the first and second

trimesters of pregnancy (see Toxicology).

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or the embryo-foetal

development. Data from epidemiological studies suggest an increased risk of miscarriage and of

cardiac malformation after use of a prostaglandin synthesis inhibitor in early pregnancy.

In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in

increased pre- and post-implantation loss and embryo-foetal lethality. In addition, increased

incidences of various malformations, including cardiovascular, have been reported in animals

given a prostaglandin synthesis inhibitor during the organogenetic period.

Nursing Women:

(See Contraindications)

Pediatrics:

(See Contraindications)

Geriatrics (> 65 years of age):

Patients older than 65 years (referred to in this document as older or elderly) and frail or

debilitated patients are more susceptible to a variety of adverse reactions from NSAIDs. The

incidence of these adverse reactions increases with dose and duration of treatment. In addition,

these patients are less tolerant to ulceration and bleeding. Most reports of fatal GI events are in

this population, especially those with cardiovascular disease. Older patients are also at risk of

lower esophageal injury including ulceration and bleeding. For such patients, consideration

should be given to a starting dose lower than the one usually recommended, with individual

adjustment when necessary and under close supervision.

Page 14

Monitoring and Laboratory Tests

Cardiovascular: Blood Pressure should be monitored regularly during treatment with TEVA-

PIROXICAM (See Warnings and Precautions - Cardiovascular).

Hematologic: Patients should have their hemoglobin or hematocrit checked

periodically.Concurrent therapy of TEVA-PIROXICAM with warfarin requires close monitoring

of the international normalilized ratio (INR) (See Warnings and Precautions - Haematology).

Hepatic: Liver function tests should be monitored periodically (See Warnings and Precautions

Hepatic/Biliary/Pancreatic).

Opthalmologic: Opthalmic examination should be performed at periodic intervals. (See

Warnings and Precautions - Ophthalmologic).

Renal: Patients with pre-existing renal insufficiency (GFR< 60 mL/min or 1 mL/s), dehydrated

patients, patients on salt restricted diets, those with congestive heart failure, cirrhosis, liver

dysfunction, taking angiotensin-converting enzyme inhibitors, angiotensin-II receptor blocker,

cyclosporin, diuretics, and the elderly should have their renal function monitored (e.g. urine

output, serum creatinine, creatinine clearance and serum urea) during therapy with TEVA-

PIROXICAM (See Warnings and Precautions - Renal).

Serum electrolytes should be monitored periodically, especially in those patients who are at risk

(Warnings and Precautions – Renal – Fluid and Electrolyte Balance).

ADVERSE REACTIONS

Adverse Drug Reaction Overview

The most common adverse reactions encountered with nonsteroidal anti-inflammatory drugs are

gastrointestinal, of which peptic ulcer, with or without bleeding is the most severe. Fatalities have

occurred, particularly in the elderly. Evidence from epidemiological studies suggests that

piroxicam is associated with a high risk of gastrointestinal toxicity relative to some other

NSAIDs (Warnings and Precautions - Gastrointestinal).

Serious skin reactions have been associated with NSAID use. Evidence from epidemiological

studies suggests that piroxicam is associated with higher risk of serious skin reactions compared

to other non-oxicam NSAIDs (Warnings and Precautions - Skin).

Use of some NSAIDs is associated with an increased incidence of cardiovascular adverse events

(Warnings and Precautions -Cardiovascular).

Clinical Trial Adverse Drug Reactions

Because clinical trials are conducted under very specific conditions the adverse reaction

Page 15

rates observed in the clinical trials may not reflect the rates observed in practice and

should not be compared to the rates in the clinical trials of another drug. Adverse drug

reaction information from clinical trials is useful for identifying drug-related adverse

events and for approximating rates.

In approximately 2300 patients receiving a daily dose of 20 mg or less of piroxicam in clinical

trials, the most frequent side effects observed have been gastrointestinal (approximately 20% of

the patients). Of the patients experiencing gastrointestinal side effects, approximately 5%

discontinued therapy with an overall incidence of peptic ulceration of about 1% and

gastrointestinal bleeding of approximately 0.1 %. Very Common (≥10%) and Common (>1% and

≤ 10%) adverse drug reactions are summarized in Tables 1 and 2, respectively.

Table 1. Very Common (≥10%) Clinical Trial Adverse Drug Reactions

Body System

Frequency

(N≈2300)

(%)

Gastrointestinal

epigastric distress

nausea

constipation

abdominal discomfort

flatulence

diarrhea

abdominal pain

indigestion

anorexia

peptic ulceration

stomatitis

vomiting

hematemesis

melena

perforation

dry mouth

pancreatitis

17.4

About 1

< 1

< 1

< 1

< 1

< 1

< 1

< 1

Hematologic 15.0

decrease in hemoglobin

decrease in hematocrit

thrombocytopenia

eosinophilia

leukocytosis

basophilia

leukopenia

petechial rash

ecchymosis

bone marrow depression

15.0

< 1

< 1

< 1

Page 16

including aplastic anemia and

epistaxis

< 1

< 1

Table 2. Common (≥1% and ≤10%) Clinical Trial Adverse Drug Reactions

Adverse Reactions

Frequency

(N≈2300)

(%)

Central Nervous System

headache

malaise

dizziness

drowsiness/sedation (somnolence)

vertigo

depression

hallucinations

insomnia

nervousness

paresthesia

personality change

dream abnormalities

mental confusion

5

1 .8

1 .0

< 1

< 1

< 1

< 1

< 1

< 1

< 1

< 1

< 1

< 1

< 1

Dermatologic (2.0%)

rash

pruritus

erythema

bruising

desquamation

exfoliative dermatitis

erythema multiforme

toxic epidermal necrolysis

vesiculo bullous reaction

onycholysis

Stevens-Johnson syndrome

photoallergic skin reactions

2.0

< 1

< 1

< 1

< 1

< 1

< 1

< 1

< 1

< 1

< 1

< 1

Renal

(See Warnings and Precautions)

oedema

dysuria

hematuria

proteinuria

interstitial nephritis

renal failure

hyperkalemia

glomerulitis

1

< 1

< 1

< 1

< 1

< 1

< 1

< 1

Page 17

nephrotic syndrome

< 1

Special Populations: Patients older than 65 years and frail or debilitated patients are more

susceptible to a variety of adverse reactions from NSAIDs. The incidence of these adverse

reactions increases with dose and duration of treatment. In addition, these patients are less

tolerant to ulceration and bleeding. Most reports of fatal GI events are in this population. Older

patients are also at risk of lower esophageal injury, including ulceration and bleeding.

Less Common Clinical Trial Adverse Drug Reactions (<1%)

Allergic (<1%): anaphylaxis, bronchospasm, urticaria/angioedema, vasculitis, serum sickness

(see WARNINGS AND PRECAUTIONS), each in less than 1% of patients.

Cardiovascular (<1%): hypertension, palpitations, worsening of congestive heart failure (see

WARNINGS AND PRECAUTIONS, Cardiovascular), exacerbation of angina, each in less than

1 % of patients.

Special Senses: Eyes, ears, nose and throat reactions (< 1 %): tinnitus (about 1%); blurred vision,

eye irritation/swelling, each in less than 1% of patients.

Hepatic (<1%): jaundice, hepatitis (see WARNINGS AND PRECAUTIONS, Hepatic/Biliary/

Pancreatic), each in less than 1% of patients.

Respiratory (<1%): dyspnea.

Metabolic (< 1%): hypoglycemia, hyperglycemia, weight increase/decrease, each in less than 1%

of patients.

Miscellaneous (<1%): sweating, pain (colic), fever, flu-like syndrome (see WARNINGS AND

PRECAUTIONS, Skin, Infection / Aseptic Meningitis), weakness, each in less than 1 % of

patients.

Other: Isolated reports have included delayed wound healing, thrombophlebitis, pemphigus,

alopecia, mastodynia, reduction or loss of libido, impotence, urinary frequency, oliguria,

menorrhagia, amnesia, anxiety, tremor, hearing impairment, deafness, thirst, chills, increased

appetite, akathisia, tachycardia, flushing, tooth discolouration, glossitis, chest pain, anemia,

hemolytic anemia and positive antinuclear factor (ANA); a causal relationship has not been

established for these rarely reported events.

Page 18

Abnormal Hematologic and Clinical Chemistry Findings

Hematologic (15.0%): See Table 1, Very common (≥10%) Clinical Trial Adverse Drug

Reactions. See Warnings and Precautions, Hematologic.

Laboratory Parameters:

Changes in laboratory parameters observed during piroxicam therapy have included an elevation

of BUN, creatinine (see WARNINGS AND PRECAUTIONS, Renal), uric acid and liver

enzymes LDH, SGOT, SGPT and alkaline phosphatase.

Post-Market Adverse Drug Reactions

Evidence from epidemiological studies suggests that piroxicam is associated with high risk of

gastro-intestinal toxicity relative to some other NSAIDs.

Evidence from epidemiological studies suggests that piroxicam is associated with higher risk of

serious skin reaction compared to other non-oxicam NSAIDs.

In patients taking piroxicam the most frequently reported adverse experiences occurring

commonly (in 1-10% of patients) are:

Cardiovascular System

Oedema

Digestive System

Anorexia, abdominal pain, constipation, diarrhoea,

dyspepsia, elevated liver enzymes, flatulence, gross

bleeding/perforation, heartburn, nausea, ulcers,

(gastric/duodenal), vomiting

Hemic and Lymphatic System

Anaemia, increased bleeding time

Nervous System

Dizziness, headache

Skin and Appendages

Pruritus, rash

Special Senses

Tinnitus

Urogenital System

Abnormal renal function

Adverse experiences reported in 0.1% -1% of patients include:

Body as a Whole

Fever, infection, sepsis

Cardiovascular System

Congestive heart failure, hypertension, tachycardia,

syncope

Digestive System

Dry mouth, esophagitis, gastritis, glossitis,

hematemesis, hepatitis, jaundice, melena, rectal

bleeding, stomatitis

Hemic and Lymphatic System

Ecchymosis, eosinophilia, epistaxis, leukopenia,

purpura, petechial rash, thrombocytopenia

Metabolic and Nutritional

Weight changes

Nervous System

Anxiety, asthenia, confusion, depression, dream

abnormalities, drowsiness, insomnia, malaise,

Page 19

nervousness, paresthesia, somnolence, tremors,

vertigo

Respiratory System

Asthma, dyspnoea

Skin and Appendages

Alopecia, bruising, desquamation, erythema,

photosensitivity, sweat

Special Senses

Blurred vision

Urogenital System

Cystitis, dysuria, hematuria, hyperkalemia,

interstitial nephritis, nephritic syndrome,

oliguria/polyuria, proteinuria, renal failure

Other adverse reactions, which occur rarely (0.01% -<0.1%) are:

Body as a Whole

Anaphylactic reactions, appetite change, death, flu-

like syndrome, pain (colic), serum sickness

Cardiovascular System

Arrhythmia, exacerbation of angina, hypotension,

myocardial infarction, palpitations, vasculitis

Digestive System

Eructation, liver failure, pancreatitis

Hemic and Lymphatic System

Agranulocytosis, haemolytic anemia, aplastic

anemia, lymphadenopathy, pancytopenia

Metabolic and Nutritional

Hyperglycemia, hypoglycemia

Nervous System

Akathisia, convulsions, coma, hallucinations,

meningitis, mood alterations

Respiratory System

Respiratory depression, pneumonia

Skin and Appendages

Angioedema, toxic epidermal necrosis, erythema

multiforme, exfoliative dermatitis, onycholysis,

Stevens-Johnson syndrome, urticaria,

vesiculobullous reaction

Special Senses

Conjunctivitis, hearing impairment, swollen eyes

DRUG INTERACTIONS

Drug-Drug Interactions

Highly Protein Bound Drugs:

TEVA-PIROXICAM is highly protein bound, and therefore might be expected to displace other

protein-bound drugs. The physician should closely monitor dosage requirement of coumarin

anticoagulants and other drugs that are highly protein-bound when these are administered

concomitantly with TEVA-PIROXICAM.

Acetylsalicylic acid (ASA) or other NSAIDs:

The use of TEVA-PIROXICAM in addition to any other NSAID, including over the counter one

(such as ASA and ibuprofen) for analgesic and/or anti-inflammatory effects is NOT

recommended because of the absence of any evidence demonstrating synergistic benefits and the

potential for additive side reactions.

The exception is the use of low dose ASA for cardiovascular protection, when another NSAID is

being used for its analgesic/anti-inflammatory effect, keeping in mind that combination NSAID

Page 20

therapy is associated with additive adverse reactions, and that NSAIDs may interfere with the

anti-platelet effects of low dose ASA, possibly by competing with ASA for access to the active

site of cyclooxygenase-1.

Anti-coagulants:

(See Warnings and Precautions – Hematologic - Anti-coagulants)

Numerous studies have shown that the concomitant use of NSAIDs and anticoagulants increases

the risk of GI adverse events such as ulceration and bleeding. Because prostaglandins play an

important role in hemostasis, and NSAIDs affect platelet function, concurrent therapy of TEVA-

PIROXICAM with warfarin requires close monitoring to be certain that no change in

anticoagulant dosage is necessary. TEVA-PIROXICAM is highly protein-bound, and therefore,

might be expected to displace other protein-bound drugs. The physician should closely monitor

dosage requirements of coumarin anticoagulants and other drugs that are highly protein-bound

when these are administered concomitantly with TEVA-PIROXICAM.

Anti-hypertensives:

NSAIDs may diminish the anti-hypertensive effect of Angiotensin Converting Enzyme (ACE)

inhibitors.

Combinations of ACE inhibitors, angiotensin-II antagonists, or diuretics and NSAIDs might have

an increased risk for acute renal failure and hyperkalemia. Blood pressure and renal function

(including electrolytes) should be monitored more closely in this situation, as occasionally there

can be a substantial increase in blood pressure.

Concomitant administration of TEVA-PIROXICAM with propranolol can reduce the

hypotensive effect. Patients should be monitored for altered antihypertensive or antianginal

response to betablockers when TEVA-PIROXICAM is initiated or discontinued.

Anti-platelet Agents (including ASA):

There is an increased risk of bleeding, via inhibition of platelet function, when anti-platelet

agents are combined with NSAIDs, such as TEVA-PIROXICAM (see Warnings and

Precautions – Hematologic - Anti-platelet Effects).

Cholestyramine:

In healthy subjects co-administration of cholestyramine to piroxicam results in enhanced

elimination of piroxicam (i.e. reduction in half-life by 40% and increase in clearance by 52%).

Although the magnitude of these changes in piroxicam disposition appears sufficient to inhibit its

therapeutic effects, studies in patients are needed to confirm this. It is suggested that the doses of

TEVA-PIROXICAM and cholestyramine be separated as much as possible, and that the patients

be monitored for inadequate response to piroxicam therapy. If an inadequate anti-inflammatory

response appears to be related to the concomitant use of cholestyramine, consideration should be

given to the use of alternative hypolipidemic therapy.

Page 21

Cimetidine:

Results of two separate studies indicate a slight increase in absorption of piroxicam following

cimetidine administration but no significant changes in elimination parameters. Cimetidine

increases the area under the curve (AUC 0-120 hrs) and Cmax of piroxicam by approximately 13

to 15%. Elimination rate constants and half-life show no significant differences. The clinical

significance of this small but significant increase in absorption is yet unknown.

Cyclosporin:

Inhibition of renal prostaglandin activity by NSAIDs may increase the plasma concentration of

cyclosporin and/or the risk of cyclosporin induced nephrotoxicity. Patient should be carefully

monitored during concurrent use.

Diuretics:

Clinical studies as well as post-marketing observations have shown that NSAIDs can reduce the

effect of diuretics. During concomitant therapy with NSAIDs, the patient should be closely

observed for signs and symptoms of renal failure (Warnings and Precautions - Renal) as well

as to assess diuretic efficacy.

Glucocorticoids:

Some studies have shown that the concomitant use of NSAIDs and oral glucocorticoids increases

the risk of GI adverse events such as ulceration and bleeding. This is especially the case in older

(> 65 years of age) individuals.

Lithium:

Piroxicam has been reported to increase steady state plasma lithium concentrations. It is

recommended that these concentrations are monitored when initiating, adjusting and

discontinuing TEVA-PIROXICAM treatment.

Methotrexate:

Although up to date there have been no reports of an interaction with piroxicam, isolated cases

indicate that the concomitant use of some NSAIDs in patients receiving methotrexate may be

associated with severe or sometimes fatal methotrexate toxicity.

Until more information is available on this interaction, caution should be used if TEVA-

PIROXICAM is administered concomitantly with methotrexate, particularly in patients with pre

existing renal impairment, who may be more susceptible.

Selective Serotonin Reuptake Inhibitors (SSRIs):

Concomitant administration of NSAIDs and SSRIs may increase the risk of gastrointestinal

ulceration and bleeding (see Warnings and Precautions - Gastrointestinal).

Page 22

Tacrolimus:

Inhibition of renal prostaglandin activity by NSAIDs may increase the plasma concentration of

tacrolimus and/or the risk of tacrolimus induced nephrotoxicity. Patient should be carefully

monitored during concurrent use.

Oral Contraceptives:

No drug interaction information is available for TEVA-PIROXICAM co-administered with oral

contraceptives.

Oral Hypoglycemics:

An interaction has been noted with some NSAIDs, however no interaction data are available for

the co-administration of these agents with TEVA-PIROXICAM.

Drug-Food Interactions

Interactions with food have not been established.

Drug-Herb Interactions

Interactions with herbal products have not been established.

Drug-Laboratory Test Interactions

Interactions with laboratory tests have not been established.

Drug-Lifestyle Interactions

Concurrent use of alcohol with TEVA-PIROXICAM may increase the risk of gastrointestinal

side

effects, including ulceration and haemorrhage.

Smoking has been associated with an increased risk of gastrointestinal side effects, including

ulceration and bleeding.

Patients experiencing visual disturbances, dizziness, vertigo, somnolence or other central nervous

system disturbances while taking TEVA-PIROXICAM should exercise caution in carrying out

activities

that require alertness and should refrain from driving or using machines.

DOSAGE AND ADMINISTRATION

Dosing Considerations

Frail or debilitated patients may tolerate side effects less well and therefore special care should be

taken in treating this population. To minimize the potential risk for an adverse event the lowest

effective dose should be used for the shortest possible duration. As with other NSAIDs, caution

should be used in the treatment of elderly patients who are more likely to be suffering from

impaired renal, hepaticor cardiac function. Consideration should be given to a starting dose that is

lower than usual and to an increase of the dose only if symptoms remain uncontrolled. Such

Page 23

patients must be carefully supervised. For high risk patients, alternate therapies that do not

involve NSAIDs should be considered.

Hepatic Insufficiency: A substantial portion of piroxicam elimination occurs by hepatic

metabolism. Consequently, patients with hepatic disease may require reduced doses of TEVA-

PIROXICAM. TEVA-PIROXICAM is contraindicated in severe liver impairment or active liver

disease.

Renal Insufficiency: Because of the extensive renal excretion of TEVA-PIROXICAM and its

biotransformation products (less than 5% of the daily dose excreted unchanged), lower doses of

TEVA-PIROXICAM should be anticipated in patients with impaired renal function and they

should be carefully monitored. TEVA-PIROXICAM is contraindicated in severe renal

impairment and in deteriorating renal disease (See Contraindications).

Recommended Dose and Dose Adjustment

Use of TEVA-PIROXICAM should be limited to the lowest effective dose for the shortest

possible duration of treatment (See Contraindications and Warnings and Precautions)

The recommended starting dose is a single daily dose of 20 mg, or 10 mg b.i.d.

In rheumatoid arthritis and ankylosing spondylitis most patients will be maintained on 20 mg

daily. Some patients may be maintained on 10 mg daily.

In osteoarthritis the usual maintenance dose is 10-20 mg daily.

The total daily dose of TEVA-PIROXICAM should not exceed 20 mg per day.

TEVA-PIROXICAM capsules should be taken immediately after a meal or with food or milk. If

stomach upset (indigestion, nausea, vomiting, stomach pain or diarrhea) occurs and continues, a

doctor should be consulted.

Hepatic Insufficiency: (See Dosing Considerations).

Renal Insufficiency: (See Dosing Considerations).

Geriatrics (>65 years of age), Frail or Debilitated: (See Dosing Considerations).

Pediatrics (<16 years of age): (See Contraindications).

Page 24

Missed Dose

If a dose of TEVA-PIROXICAM is taken once a day and a dose of this medicine is missed, a

dose of TEVA-PIROXICAM should be taken right away if remembered by the patient within 8

hours of the missed dose. If TEVA-PIROXICAM is taken twice a day and a dose is missed,

which the patient remembers within 2 hours of the missed dose then the dose should be taken

right away and the patient should go back to the regular dosing schedule.

OVERDOSAGE

For management of a suspected drug overdose, contact your regional Poison Control Centre.

Cases of overdose, up to l800 mg piroxicam, have been reported. Recovery was complete without

sequelae. In the event of overdosage with TEVA-PIROXICAM (piroxicam) supportive and

symptomatic therapy is indicated. Studies indicate that administration of activated charcoal may

result in reduced absorption and reabsorption of piroxicam thus reducing the total amount of

active drug available.

Piroxicam is highly protein bound, therefore dialysis of this drug is not feasible as a course of

action due to an overdosage.

ACTION AND CLINICAL PHARMACOLOGY

Mechanism of Action

TEVA-PIROXICAM inhibits the activity of prostaglandin synthetase. The resulting decrease in

prostaglandin biosynthesis may partially explain its anti-inflammatory action. TEVA-

PIROXICAM does not act by pituitary-adrenal stimulation.

In rheumatoid arthritis the efficacy of piroxicam 20 mg daily has been found to be similar to

4.2 g daily of acetylsalicylic acid (ASA).

Pharmacodynamics

TEVA-PIROXICAM is a non-steroidal anti-inflammatory agent with analgesic and antipyretic

properties. Its mechanism of action is incompletely known. (See Action and Clinical

Pharmacology, Mechanism of Action).

Pharmacokinetics

Absorption:

Piroxicam is well absorbed following oral administration. After a single oral dose of 20 mg, peak

plasma levels of piroxicam are achieved in about 4 hours. When the drug is administered daily,

plasma concentrations increase for seven to twelve days during which a steady state is reached.

Concentrations attained are not exceeded following further constant daily drug intake. The

Page 25

plasma half- life is approximately 50 hours in man. The extent and rate of absorption are not

influenced by administration with food or antacids.

Distribution:

Ninety-nine percent of plasma piroxicam is bound to plasma proteins. The presence of piroxicam

in breast milk has been determined during initial and long term dosing conditions (52 days).

Piroxicam appeared in breast milk at about 1% to 3% of the maternal plasma concentration. No

accumulation of piroxicam occurred in milk relative to that in plasma during treatment.

Metabolism:

Piroxicam is extensively metabolized and less than 5% of the daily dose is excreted unchanged in

urine and feces. The main metabolic pathway is hydroxylation of the pyridyl ring, followed by

conjugation with glucuronic acid and urinary elimination. Approximately 5% of the dose is

metabolized to and excreted as saccharin.

Excretion:

Approximately 5% of the dose is metabolized to and excreted as saccharin.

Over a four day period of observation, twenty healthy men, taking piroxicam 20 mg daily in

single or divided doses, showed significantly less mean daily fecal blood loss than did ten healthy

male controls taking 3.9 g of ASA daily.

Special Populations and Conditions

Gender / Geriatrics: The effects of age and sex on the pharmacokinetics of piroxicam have been

examined in three single-dose, three multiple dose, and five therapeutic drug monitoring studies.

Although not consistent across all studies, some indicated a tendency towards a modest decrease

in total body clearances and an increase in elimination half-life and steady-state plasma

concentrations in the elderly, particularly elderly females. Irrespective of age, some patients had

plasma concentration levels that are substantially greater than the mean.

Hepatic Insufficiency: A substantial portion of piroxicam elimination occurs by hepatic

metabolism. Consequently, patients with hepatic disease may require reduced doses of TEVA-

PIROXICAM. TEVA-PIROXICAM is contraindicated in severe liver impairment or active liver

disease.

Renal Insufficiency: Because of the extensive renal excretion of TEVA-PIROXICAM and its

biotransformation products, lower doses of TEVA-PIROXICAM should be anticipated in

patients with impaired renal function and they should be carefully monitored. TEVA-

PIROXICAM is contraindicated in severe renal impairment and in deteriorating renal disease.

STORAGE AND STABILITY

TEVA-PIROXICAM (piroxicam) capsules should be protected from light and stored at room

temperature (15 - 30ºC) The unit dose boxes should be stored at a temperature not exceeding

Page 26

25ºC and protected from light and high humidity.

DOSAGE FORMS, COMPOSITION AND PACKAGING

TEVA-PIROXICAM 10 mg and 20 mg capsules contain the active ingredient piroxicam. The

non-medicinal ingredients are magnesium stearate, sodium lauryl sulphate, sodium starch

glycolate and starch. The 10 mg capsule is a maroon/blue opaque hard gelatin capsule and the 20

mg capsule is a maroon opaque hard gelatin capsule, both comprised of FD&C Blue #1, FD&C

Red #3 and titanium dioxide.

TEVA-PIROXICAM 10 mg and 20 mg capsules are available in bottles of 100, 250 and 500 and

also in unit dose boxes of 100.

Page 27

PART II: SCIENTIFIC INFORMATION

PHARMACEUTICAL INFORMATION

Drug Substance

Common name:

Piroxicam

Chemical name:

2H-1,2-benzothiazine-3-carboxamide, 4 hydroxy-2-methyl-N-2-

pyridinyl-1,1-dioxide

Molecular formula:

Molecular mass:

331.35

Structural formula:

Physicochemical properties: Piroxicam is a white, crystalline, hygroscopic solid. Melting

point is 196 - 200ºC. It is poorly soluble in water, dilute

acid and most organic solvents and slightly soluble in

alcohols and aqueous alkaline solution.

Piroxicam belongs to the chemical class of N-heterocyclic

carboxamides of 1,2-benzothiazine-1,1-dioxide(oxicams).

An amphoteric compound, piroxicam has a weakly acidic 4-

hydroxy proton (pKa 5.1) and a weakly basic pyridyl

nitrogen (pKa 1.5) as determined by ultraviolet absorption

spectrophotometry in methanol:water (2.5:97.5 v/v) solvent

medium.

Page 28

CLINICAL TRIALS

Bioavailability

A comparative two-way, single dose bioavailability study was performed on TEVA-

PIROXICAM 20 mg Capsules and FELDENE 20 mg Capsules. The pharmacokinetic data (mean

± standard deviation) for the two formulations is tabulated below:

Piroxicam

(1 x 20 mg)

From measured data

Arithmetic Mean (± Standard Deviation)

Parameter

Test

*

Reference

% Ratio of

Arithmetic Means

0-144

(µg*h/mL)

135.99 ± 43.95

139.90 ± 47.28

98.8 ± 16.0

(µg/mL)

2.18 ± 0.31

2.24 ± 0.39

99.50 ± 15.03

1.34 ± 0.60

1.25 ± 0.55

56.35 ± 33.21

56.11 ± 41.84

(1/h)

0.019 ± 0.021

0.023 ± 0.024

TEVA-PIROXICAM 20 mg Capsules (Novopharm Limited, Canada)

FELDENE 20 mg Capsules (Pfizer Canada Inc., Canada), purchased in Canada

DETAILED PHARMACOLOGY

Animal Studies:

The anti-inflammatory activity of piroxicam, given orally, has been demonstrated in rats, guinea

pigs and dogs. At 4.0 mg/kg dose given to rats produced 50% inhibition of carageenan-induced

foot edema. Piroxicam at doses of 0.3-3.3 mg/kg also caused inhibition of adjuvant-induced

arthritis in rats. At doses of 10 and 18 mg/kg, an inhibition of cotton string-induced granuloma

formation in rats was observed. At 0.3 mg/kg dose of piroxicam given to guinea pigs produced

50% inhibition of the erythema induced by ultraviolet light. Intravenous administration of

piroxicam (5 mg/kg) to dogs inhibited urate-induced inflammation of knee joints.

The analgesic activity of piroxicam, at an oral dose of 1.85 mg/kg, was demonstrated in mice

using the phenylquinone-induced writhing test. Piroxicam at 1.0, 3.2 and 10.0 mg/kg orally was

active in the Randall-Sellito test in which painful pressure is applied to the inflamed foot pad of

the rat. It was inactive in hot-plate and tail-flick tests at oral doses up to 100 mg/kg.

The antipyretic activity of piroxicam at 10 mg/kg orally was demonstrated in the hyperpyrexia

induced in rats by intramuscular injections of E.coli lipopolysaccharide.

Page 29

Piroxicam inhibits prostaglandin synthetase, thereby reducing the biosynthesis of prostaglandins.

The drug also inhibits collagen-induced platelet aggregation. The anti-inflammatory activity of

piroxicam does not depend upon adrenal stimulation. Its activity was demonstrated in

adrenalectomized rats. Piroxicam has no significant cardiovascular or central nervous system

activity.

Human Studies:

See Actions and Clinical Pharmacology Section.

TOXICOLOGY

Acute Toxicity:

LD

50

(95% Confidence Limits) mg/kg

Species

Sex

Oral

I.P.

Mice

360 (321-404)

360 (305-425)

approx. 360

270 (231-316)

220 (197-241)

Toxic effects observed in mice and rats included ataxia, depression, laboured respiration,

prostration, weight gain inhibition and weight loss. Necropsy of these animals revealed marked

visceral adhesions and erosions of the stomach and intestines.

In the dog, repeated emesis, chronic anorexia, and diarrhea occurred at dosage levels of 5, 25, 50,

400 and 700 mg/kg; fecal occult blood was observed 24 hours after dosing. A weight loss of

about 15% and bloody diarrhea occurred with the 50, 400 and 700 mg/kg doses. Necropsy of the

dogs receiving 5 mg/kg revealed mucosal erosions and hemorrhage. These lesions, together with

ulcerations of the pyloric antrum and/or sphincter, were also observed at the higher dose level.

Subacute and Chronic Toxicity:

Piroxicam administered orally to beagle dogs at a dose of 1.0 mg/kg/day for 373 consecutive

days caused signs of gastrointestinal and renal toxicity. These included emesis, diarrhea,

duodenal and gastric ulceration or erosion, fecal occult blood, anemia, proteinuria, hematuria,

renal papillary necrosis and one case of pyelonephritis. Other effects considered to be related to

the primary pathology were integumental signs, leukocytosis and decreased serum calcium levels.

Page 30

A one year study in the rhesus monkey at daily oral doses of 2.5, 5.0 and 10.0 mg/kg revealed

epithelial casts within the collecting tubules of the kidneys in 67% of high dose females. There

was no evidence of gastrointestinal toxicity at any dose. Another study in rhesus monkeys was

conducted over 90 days at the same dose levels. Occasional erosions of the gastrointestinal

mucosa were observed only in the animals receiving the highest dose. However, one female

monkey, receiving 2.5 mg/kg/day did develop an acute gastric ulcer.

In an 18 month rat study, daily oral doses of 0.3, 1.0 and 3.0 mg/kg gave dose- and duration-

related renal papillary necrosis, elevation of BUN and necrotizing gastrointestinal lesions. At the

highest dose, gastrointestinal lesions and renal papillary necrosis were present in more females

than males. Dose-related anemia in males also occurred.

An 18 month mouse study was conducted at daily oral doses of 2, 4 and 8 mg/kg. There was

increased mortality at 8 mg/kg. Dose-related renal papillary necrosis with secondary chronic

diffuse interstitial nephritis, elevated BUN and necrotizing gastrointestinal lesions were observed.

Reproduction and Teratology Studies:

Consistent with its inhibitory effect on prostaglandin biosynthesis, piroxicam prolongs the

gestational period of the rat. The effects are dependent on dose and time.

When piroxicam was administered in oral doses of 2, 5 and 10 mg/kg daily to pregnant rats from

day 15 post-coitum onwards, a dose-dependent increase in mortality and prolongation of

gestation and parturition occurred. Parturition was completely inhibited by piroxicam at 10

mg/kg administered for 8 days. The dystocia, together with the gastrointestinal toxicity of the

drug, caused weakness and death of dams and offspring. When treatment was stopped after 5

days of drug administration, deaths and prolonged labour still occurred.

When pregnant rats received 10 mg/kg/day of piroxicam orally from day 1 post-coitum to day 16,

17, 18, 19 or 20 post-coitum, all groups displayed gestational prolongation and the delay

increased with length of treatment. Prolongation of parturition and increased mortality of the

offspring occurred. There was dose-related suppression of lactation.

Piroxicam was administered in oral doses of 2, 5 and 10 mg/kg/day to male and female rats for

81 and 14 days respectively, before mating. Dosing in females was continued to day 6 post-

coitum. Neither sex exhibited a modification of sexual behaviour or diminished fertility. Fetal

development was normal. Viability and growth of pups were comparable to controls, and no

drug-induced malformation or lesion was seen.

Oral administration of piroxicam to pregnant rats and rabbits, during the critical period of

organogenesis, induced no embryotoxic or teratogenic effect at doses of 2, 5 and 10 mg/kg/day.

Page 31

Oral administration of piroxicam to female rats on days 1-12 of the lactation period inhibited

postnatal body weight gain in pups owing to suppression of lactation in dams. This effect was

explored at doses of 2, 5 and 10 mg/kg/day and was dose-related.

Mutagenicity:

Piroxicam demonstrated no mutagenic activity in any of the test systems.

Carcinogenicity:

In a 24-month rat study, piroxicam administered in the diet to provide doses of 0.3 and 1.0

mg/kg, induced the same spectrum, but higher incidence at 1 mg/kg, of non-neoplastic lesions

than in the 18- month rat study. The principal drug induced pathologic changes consisted of renal

papillary necrosis, suppurative pyelonephritis and pyloric ulceration. Except for suppurative

pyelonephritis, females were more often affected than males.

Page 32

REFERENCES

1. Anti-inflammatory Analgesics, Nonsteroidal (Systemic). United States Pharmacopoeia

Dispensing Information Drug Information for the Health Care Professional Twelfth edition

1992. IA:460-469, 479.

2. Brogden R. C. Heel R.C.; Speight T.M.; Avery G.S.; Piroxicam: A reappraisal of its

pharmacology and therapeutic efficacy. Drugs 28:292-323 (1984).

3. Caille G. and Vezina M, Comparative bioavailability study of Piroxicam 20 mg suppositories

1990. Data on file at Pharmascience Inc. (Part III, Vol. 4 p. 43-44; Part IV, Vol. 5 p. 1-17).

4. Dessain P, Estabrooks TF, Gordon AJ. Piroxicam in the treatment of osteoarthritis: a multi-

centre study in general practice involving 1218 patients. J Int Med Res 1979; 7:335-34.

5. FELDENE (piroxicam) 10 and 20 mg Capsules and Suppositories Product Monograph. Pfizer

Canada Inc. Date of Preparation: April 1, 1981, Date of Revision: August 24, 1993.

6. Heynen G; Dessain P.: Piroxicam Suppositories for osteoarthritis and rheumatoid arthritis: an

open multicentre study in 116 patients. Eur. J. Rheum. Inflam., 6:134-138 (1983).

7. Hobbs D.C., Gordon A.J.: Absense of an effect of age on the pharmacokinetics of piroxicam.

Roy. Soc. Med. Int. Congr. Symp. Series 67:270-281, 1979.

8. Hobbs D.C., Twomey TM. Piroxicam pharmacokinetics in man: aspirin and antacid

interaction studies. J Clin Pharmacol 1979; 219:270-281.

9. Neuman M.: A clinical and pharmacokinetic study of piroxicam administered as a rectal

suppository. Drugs Exptl. Clin, res VII(1):15-24 (1981).

10. Nuotio P. and Makisara P.: Pharmacokinetic and clinical study of piroxicam. Royal Society

of Medicine International Congress and Symposium Series No. 1:25-30 (1978).

11. Piroxicam. Martindale The Extra Pharmacopoeia Twenty-ninth edition 1989. London. The

Pharmaceutical Press. 37-39.

12. Pisko EJ, Rahman MA, Turner RA, Agudelo CA. Long-term efficacy and safety or piroxicam

in the treatment of rheumatoid arthritis. Curr Ther Res 1980; 27:852-859.

13. Pitts N.E.: Efficacy and safety of piroxicam. Am. J. Med. 72(2A):77-78, 1982.

14. Radi I.; Matoso L.; Posmantir A. and Papalexiou P.: Safety and efficacy of piroxicam in the

treatment of ankylosing spondylitis. Eur. J. Rheum. Inflam., 1:346-351 (1978).

15. Richardson JC, Block KLN, Ross SG, Verbeeck RK. Effects of age and sex on piroxicam

disposition. Clin Pharmacol Ther 1985; 37:13-18.

Page 33

16. Schiantarelli P.; Cadel S.: Piroxicam pharmacologic activity and gastrointestinal damage by

oral and rectal route. Comparison with oral indométhacine and phenylbutazone.

Forsch./Drugs Res. 31(1): No. 1 (1981).

17. Schiantarelli P.; Acerbi D.; Bovis G.: Some pharmacokinetic properties and bioavailability by

oral and rectal route of piroxicam in rodents and in man. Drug res. 31(1), No. 1 (1981).

18. Steigerwald J.C.: Piroxicam and rheumatoid arthritis: a double blind 16-week study

comparing piroxicam and indométhacine. Royal Society of Medicine International Congress

and Symposium Series No. 1:47-52 (1978).

19. Ward J.R.; Willkens R.F.; Louie J.S; McAdam L.P.: Piroxicam and rheumatoid arthritis: A

multi-center 14 week controlled double-blind study comparing aspirin and piroxicam. Roy.

Soc. Med. Int. Congr. Symp. Series 1:31-39 (1978).

20. Wiseman E.H. and Boyale J.A.: Piroxicam (Feldene). Clinics in Rheumatic Diseases 6:585-

613 (1980).

21. Wiseman E.H.: Review of preclinical studies with piroxicam, pharmacokinetics, and

toxicology. Roy. Soc. Med. Int. Congr. Symp. Series 1:11-23 (1978).

22. Wiseman E.H., Chang Y-H, Lombardino JG. Piroxicam, a novel anti-inflammatory agent.

Arzneim-Forsch 1976; 26:1300-1303.

23. Woolf AD, Rogers HJ, Bradbrook ID, Corless D. Pharmacokinetic observations on piroxicam

in young adult, middle-aged and elderly patients. Br J Clin Pharmac 1983; 16:433-437.

24. Basic Product Monograph Information for Nonsteroidal Anti-Inflammatory Drugs

(NSAIDs), Guidance Document, Health Products and Food Branch, November 23, 2006.

Comparative Bioavailability Study of Piroxicam in Human Volunteers, November 12, 1984.

Data on file at Novopharm Limited.

IMPORTANT: PLEASE READ

Page 34

PART III: CONSUMER INFORMATION

Pr

TEVA-PIROXICAM

(piroxicam)

Read this information each time you refill your prescription

in case new information has been added. This leaflet is part III

of a three-part “Product Monograph" published when TEVA-

PIROXICAM was approved for sale in Canada and is designed

specifically for Consumers. This leaflet is a summary and will not

tell you everything about TEVA-PIROXICAM. Contact your

doctor or pharmacist if you have any questions about the drug.

ABOUT THIS MEDICATION

What the medication is used for:

Your health care provider has prescribed TEVA-PIROXICAM for

you for symptomatic relief of one or more of the following

medical conditions:

rheumatoid arthritis

osteoarthritis (degenerative joint disease)

ankylosing spondylitis

What it does:

TEVA-PIROXICAM (piroxicam) a nonsteroidal anti-

inflammatory drug (NSAID), can reduce the chemicals produced

by your body, which cause pain and swelling.

TEVA-PIROXICAM does NOT cure your illness or prevent it

from getting worse. TEVA-PIROXICAM can only relieve the

pain and reduce swelling as long as you continue to take it.

When it should not be used:

DO NOT TAKE TEVA-PIROXICAM if you have any of the

following medical conditions:

Heart bypass surgery (planning to have or recently

had)

Severe, uncontrolled heart failure

Bleeding in the brain or other bleeding disorders

Current pregnancy (after 28 weeks of pregnancy)

Currently breastfeeding (or planning to breastfeed)

Allergy to ASA (Acetylsalicylic Acid) or other

NSAIDs (Nonsteroidal Anti- Inflammatory Drugs)

Ulcer (active)

Bleeding from the stomach or gut (active)

Inflammatory bowel disease (Crohn’s Disease or

Ulcerative Colitis)

Liver disease (active or severe)

Kidney disease (severe or worsening)

High potassium in the blood

Allergy to piroxicam or to any ingredient in the

formulation (see nonmedicinal ingredients below).

Patients who took a drug in the same class as TEVA-

PIROXICAM after a type of heart surgery (coronary artery

bypass grafting (CABG)) were more likely to have heart

attacks, strokes, blood clots in the leg(s) or lung(s), and

infections or other complications than those who did NOT

take that drug.

TEVA-PIROXICAM should NOT be used in patients under

16years of age since the safety and effectiveness have NOT been

established.

What the medicinal ingredient is:

Piroxicam

What the nonmedicinal ingredients are:

Magnesium stearate, sodium lauryl sulphate, sodium starch

glycolate and starch.

10mg and 20mg capsules: FD&C blue#1, FD&C red #3 and

titanium dioxide.

What dosage forms it comes in:

TEVA-PIROXICAM is available in 10 mg and 20 mg capsules.

WARNINGS AND PRECAUTIONS

If you have, or previously had, any of the following medical

conditions, see your health care provider to discuss

treatment options other than TEVA-PIROXICAM:

Heart Attack or Angina

Stroke or Mini-stroke

Loss of Vision

Current Pregnancy (less than 28 weeks)

Congestive Heart Failure

Gastrointestinal conditions such as ulcers, stomach

bleeding, obstructions

Kidney problems (i.e. sodium retention) leading to

increase blood pressure

Before taking this medication, tell your health care provider if you

have any of the following:

High blood pressure

High cholesterol

Diabetes mellitus or on a low sugar diet

Atherosclerosis

Poor circulation to your extremities

Smoker or ex-smoker

Kidney disease or urine problems

Previous ulcer or bleeding from the stomach or gut

Previous bleeding in the brain

Bleeding problems

Family history of asthma, nasal polyps, long-term swelling

of the sinus (chronic sinusitis) or hives

IMPORTANT: PLEASE READ

Page 35

Family history of allergy to piroxicam or other NSAIDs,

such as acetylsalicylic acid (ASA), celecoxib, diclofenac,

diflunisal, etodolac, fenoprofen, flurbiprofen, ibuprofen,

indomethacin, ketoprofen, ketorolac, mefenamic acid,

meloxicam, nabumetone, naproxen, oxaprozin, piroxicam,

rofecoxib, sulindac, tenoxicam, tiaprofenic acid, tolmetin, or

valdecoxib (NOT a complete list)

Any other medical problem.

Also, before taking this medication, tell your health care provider

if you are planning to get pregnant.

While taking this medication:

tell any other doctor, dentist, pharmacist or other health

care professional that you see, that you are taking this

medication, especially if you are planning to have heart

surgery;

do NOT drink alcoholic beverages while taking this

medication because you would be more likely to

develop stomach problems;

Fertility may be decreased. The use of TEVA-

PIROXICAM is not recommended in women trying to

get pregnant. In women who have difficulty conceiving,

stopping TEVA-PIROXICAM should be considered.

Check with your doctor if you are not getting any relief

or if any problems develop.

Your regular medical checkups are essential.

INTERACTIONS WITH THIS MEDICATION

Talk to your health care provider and pharmacist if you are taking

any other medication (prescription or non-prescription) such as

any of the following (NOT a complete list):

Acetylsalicylic Acid (ASA) or other NSAIDs

e.g. ASA, celecoxib, diclofenac, ibuprofen, indomethacin,

ketorolac, meloxicam, naproxen

Antidepressants

- Selective Serotonin Reuptake Inhibitors (SSRIs)

e.g. citalopram, fluoxetine, paroxetine, sertraline

Blood pressure medications

- ACE (angiotensin converting enzyme) inhibitors

e.g. enalapril, lisinopril, perindopril, ramipril

- ARBs (angiotensin II receptor blockers)

e.g. candesartan, irbesartan, losartan, valsartan

- Beta-adrenergic blockers

e.g. propranolol

Blood thinners

e.g. warfarin, ASA, clopidogrel

Cimetidine

Cholestyramine

Corticosteroids (including glucocorticoids)

e.g. prednisone

Cyclosporin

Digoxin

Diuretics

e.g. furosemide, hydrochlorothiazide

Lithium

Methotrexate

Oral contraceptives

Oral hypoglycemics (diabetes medications)

Tacrolimus

Your health care provider may prescribe low dose ASA

(acetylsalicylic acid) as a blood thinner to reduce your risk of

having a heart attack or stroke while you are taking TEVA-

PIROXICAM. Take only the amount of ASA prescribed by your

health care provider. You are more likely to upset or damage your

stomach if you take both TEVA-PIROXICAM and ASA than if

you took TEVA-PIROXICAM alone.

PROPER USE OF THIS MEDICATION

Usual dose:

Medical

Condition

Starting Dose

Maximum

Dose

( per day)

Rheumatoid

arthritis

20 mg once daily or 10 mg

twice daily. According to

therapeutic response, the

dose may be reduced to 10

mg once daily

20 mg

Ankylosing

spondylitis

20 mg once daily or 10 mg

twice daily. According to

therapeutic response, the

dose may be reduced to 10

mg once daily

20 mg

Osteoarthritis

20 mg once daily or 10 mg

twice daily. According to

therapeutic response, the

20 mg

IMPORTANT: PLEASE READ

Page 36

dose may be reduced to 10

mg once daily

Take TEVA-PIROXICAM only as directed by your health care

provider. Do NOT take more of it, do

NOT take it more often

and do NOT take it for a longer period of time than your

health care provider recommended. If possible, you should

take the lowest dose of this medication for the shortest time

period. Taking too much TEVA-PIROXICAM may increase your

chances of unwanted and sometimes dangerous side effects,

especially if you are elderly, have other diseases or take other

medications.

See your health care provider regularly to discuss whether this

medicine is working for you and if it is causing you any unwanted

effects.

This medication has been prescribed specifically for you. Do

NOT give it to anyone else. It may harm them, even if their

symptoms seem to be similar to yours.

TEVA-PIROXICAM is NOT recommended for use in

patients under 16 years of age since safety and effectiveness

have NOT been established.

TEVA-PIROXICAM must be taken immediately after a meal or

with food or milk.

Missed Dose:

If you take TEVA-PIROXICAM (piroxicam) once a day and if

you miss a dose of this medicine and remember within 8 hours of

the missed dose, take it right away. If you take TEVA-

PIROXICAM (piroxicam) twice a day and if you miss a dose and

remember within 2 hours of the missed dose take it right away.

Then go back to your regular dosing schedule.

Overdose:

If you take more than the prescribed dose, contact a health care

practitioner, hospital emergency department or regional Poison

Control Center immediately, even if there are no symptoms.

SIDE EFFECTS AND WHAT TO DO ABOUT THEM

TEVA-PIROXICAM may cause some side effects, especially

when used for a long time or in large doses. When these side

effects occur, you may require medical attention. Report all

symptoms or side effects to your health care provider.

TEVA-PIROXICAM may cause you to become drowsy or tired.

Be careful about driving or participating in activities that require

you to be alert. If you become drowsy, dizzy or light-headed after

taking TEVA-PIROXICAM, do NOT drive or operate machinery.

TEVA-PIROXICAM may cause you to become more sensitive to

sunlight. Any exposure to sunlight or sunlamps may cause

sunburn, skin blisters, skin rash, redness, itching or

discolouration, or vision changes. If you have a reaction from the

sun, check with your health care provider.

Check with your health care provider IMMEDIATELY if you

develop chills, fever, muscle aches or pains, or other flu-like

symptoms, especially if they occur before or together with a skin

rash. These symptoms may be the first signs of a SERIOUS

ALLERGIC REACTION to this medication.

SERIOUS SIDE EFFECTS AND WHAT TO DO ABOUT

THEM

Symptom

STOP taking

TEVA-

PIROXICAM and

get emergency

medical attention

IMMEDIATELY

STOP taking

TEVA-

PIROXICAM and

talk to your

physician or

pharmacist

Bloody or black

tarry stools

Shortness of

breath, wheezing,

and trouble

breathing or chest

tightness

Skin rash, hives,

swelling or itching

Blurred vision, or

any visual

disturbance

Any change in the

amount or colour

of your urine (red

or brown)

Any pain or

difficulty

experienced while

urinating

Swelling of the feet,

lower legs; weight

gain

Vomiting or

persistent

indigestion, nausea,

stomach pain or

diarrhea

Yellow

discolouration of

the skin or eyes,

with or without

itchy skin

Malaise, fatigue,

loss of appetite

Headaches, stiff

neck

Mental confusion,

depression

IMPORTANT: PLEASE READ

Page 37

SERIOUS SIDE EFFECTS AND WHAT TO DO ABOUT

THEM

Dizziness,

lightheadedness

Hearing Problems

This is not a complete list of side effects. If you develop any other

symptoms while taking TEVA-PIROXICAM see your health care

provider.

HOW TO STORE IT

TEVA-PIROXICAM capsules should be protected from light and

stored at room temperature (15 - 30ºC). The unit dose boxes

should be stored at a temperature not exceeding 25ºC and

protected from light and high humidity.

Do NOT keep outdated medicine or medicine no longer

needed. Any outdated or unused medicine should be returned to

your pharmacist.

Keep Out of the Reach of Children.

REPORTING SUSPECTED SIDE EFFECTS

You can report any suspected adverse reactions associated with

the use of health products to the Canada Vigilance Program by

one of the following 3 ways:

-------------------------------------------------------------------

Report online at www.healthcanada.gc.ca/medeffect

Call toll-free at 1-866-234-2345

Complete a Canada Vigilance Reporting Form and:

- Fax toll-free to 1-866-678-6789, or

- Mail to: Canada Vigilance Program

Health Canada

Postal Locator 0701D

Ottawa, ON K1A 0K9

Postage paid labels, Canada Vigilance Reporting Form and the

adverse reaction reporting guidelines are available on the

MedEffect

Canada Web site at

www.healthcanada.gc.ca/medeffect.

NOTE: Should you require information related to the

management of side effects, contact your health professional.

The Canada Vigilance Program does not provide medical

advice.

MORE INFORMATION

This document plus the full product monograph, prepared for

health professionals can be found by contacting Teva Canada

Limited at:

1-800-268-4127 ext. 1255005 (English); 1-877-777-9117

(French)

or druginfo@tevacanada.com

This leaflet was prepared by:

Teva Canada Limited

30 Novopharm Court

Toronto, Ontario

Canada, M1B 2K9

Last revised: July 14, 2015

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