Piroxicam: Package Insert and Label Information

PIROXICAM- piroxicam capsule
Strides Shasun Limited

WARNING: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS

Cardiovascular Thrombotic Events

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use. [see Warnings and Precautions (5.1) ].
  • Piroxicam Capsules USP is contraindicated in the setting of coronary artery bypass graft (CABG) surgery [see Contraindications (4) and 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)].

1 INDICATIONS AND USAGE

Piroxicam Capsules USP is indicated:

  • For relief of the signs and symptoms of osteoarthritis.
  • For relief of the signs and symptoms of rheumatoid arthritis.

2 DOSAGE AND ADMINISTRATION

Carefully consider the potential benefits and risks of Piroxicam Capsules USP and other treatment options before deciding to use Piroxicam Capsules USP. Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see Warnings and Precautions (5)].

After observing the response to initial therapy with Piroxicam Capsules USP, the dose and frequency should be adjusted to suit an individual patient’s needs.

For the relief of rheumatoid arthritis and osteoarthritis, the dosage is 20 mg given orally once per day. If desired, the daily dose may be divided. Because of the long half-life of Piroxicam Capsules USP, steady-state blood levels are not reached for 7–12 days. Therefore, although the therapeutic effects of Piroxicam Capsules USP are evident early in treatment, there is a progressive increase in response over several weeks and the effect of therapy should not be assessed for two weeks.

3 DOSAGE FORMS AND STRENGTHS

Piroxicam Capsules, USP:

  • 10 mg are maroon opaque cap and blue opaque body imprinted with ‘P10′ on body
  • 20 mg are maroon opaque cap and maroon opaque body imprinted with “P20″ on body.

4 CONTRAINDICATIONS

Piroxicam Capsules USP is contraindicated in the following patients:

  • Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to piroxicam or any components of the drug product [see Warnings and Precautions (5.7, 5.9)]
  • History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients [see Warnings and Precautions (5.7, 5.8)]
  • In the setting of coronary artery bypass graft (CABG) surgery [see Warnings and Precautions (5.1)]

5 WARNINGS AND PRECAUTIONS

5.1 Cardiovascular Thrombotic Events

Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI), and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic risk has been observed most consistently at higher doses.

To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur.

There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as piroxicam, increases the risk of serious gastrointestinal (GI) events [see Warnings and Precautions (5.2)].

Status Post Coronary Artery Bypass Graft (CABG) Surgery

Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10–14 days following CABG surgery found an increased incidence of myocardial infarction and stroke. NSAIDs are contraindicated in the setting of CABG [see Contraindications (4)].

Post-MI Patients

Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment. In this same cohort, the incidence of death in the first year post-MI was 20 per 100 person years in NSAID-treated patients compared to 12 per 100 person years in non-NSAID exposed patients. Although the absolute rate of death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID users persisted over at least the next four years of follow-up.

Avoid the use of Piroxicam Capsules USP in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If Piroxicam Capsules USP is used in patients with a recent MI, monitor patients for signs of cardiac ischemia.

5.2 Gastrointestinal Bleeding, Ulceration, and Perforation

5.3 Hepatotoxicity

Elevations of ALT or AST (three or more times the upper limit of normal [ULN]) have been reported in approximately 1% of NSAID-treated patients in clinical trials. In addition, rare, sometimes fatal, cases of severe hepatic injury, including fulminant hepatitis, liver necrosis, and hepatic failure have been reported.

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

Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, diarrhea, pruritus, jaundice, right upper quadrant tenderness, and “flu-like” symptoms). If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), discontinue Piroxicam Capsules USP immediately, and perform a clinical evaluation of the patient.

5.4 Hypertension

NSAIDs, including Piroxicam Capsules USP can lead to new onset of hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. Patients taking angiotensin converting enzyme (ACE) inhibitors, thiazide diuretics, or loop diuretics may have impaired response to these therapies when taking NSAIDs [see Drug Interactions.7)].

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

5.5 Heart Failure and Edema

The Coxib and traditional NSAID Trialists’ Collaboration meta-analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared to placebo-treated patients. In a Danish National Registry study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death.

Additionally, fluid retention and edema have been observed in some patients treated with NSAIDs. Use of piroxicam may blunt the CV effects of several therapeutic agents used to treat these medical conditions (e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers [ARBs]) [see Drug Interactions (7)].

Avoid the use of Piroxicam Capsules USP in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If Piroxicam Capsules USP is used in patients with severe heart failure, monitor patients for signs of worsening heart failure.

5.6 Renal Toxicity and Hyperkalemia

Renal Toxicity

Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury.

Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of an NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors or ARBs, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.

No information is available from controlled clinical studies regarding the use of Piroxicam Capsules USP in patients with advanced renal disease. The renal effects of Piroxicam Capsules USP may hasten the progression of renal dysfunction in patients with preexisting renal disease.

Correct volume status in dehydrated or hypovolemic patients prior to initiating Piroxicam Capsules USP. Monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia during use of Piroxicam Capsules USP [see Drug Interactions (7)]. Avoid the use of Piroxicam Capsules USP in patients with advanced renal disease unless the benefits are expected to outweigh the risk of worsening renal function. If Piroxicam Capsules USP is used in patients with advanced renal disease, monitor patients for signs of worsening renal function.

Hyperkalemia

Increases in serum potassium concentration, including hyperkalemia, have been reported with use of NSAIDs, even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to a hyporeninemic-hypoaldosteronism state.

5.7 Anaphylactic Reactions

Piroxicam has been associated with anaphylactic reactions in patients with and without known hypersensitivity to piroxicam and in patients with aspirin-sensitive asthma [see Contraindications (4) and Warnings and Precautions (5.8)].

Seek emergency help if an anaphylactic reaction occurs.

5.8 Exacerbation of Asthma Related to Aspirin Sensitivity

A subpopulation of patients with asthma may have aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps; severe, potentially fatal bronchospasm; and/or intolerance to aspirin and other NSAIDs. Because cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, Piroxicam Capsules USP is contraindicated in patients with this form of aspirin sensitivity [see Contraindications (4)]. When Piroxicam Capsules USP is used in patients with preexisting asthma (without known aspirin sensitivity), monitor patients for changes in the signs and symptoms of asthma.

5.9 Serious Skin Reactions

NSAIDs, including piroxicam, can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens — Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Inform patients about the signs and symptoms of serious skin reactions, and to discontinue the use of Piroxicam Capsules USP at the first appearance of skin rash or any other sign of hypersensitivity. Piroxicam Capsules USP is contraindicated in patients with previous serious skin reactions to NSAIDs [see Contraindications (4)].

5.10 Premature Closure of Fetal Ductus Arteriosus

Piroxicam may cause premature closure of the fetal ductus arteriosus. Avoid use of NSAIDs, including Piroxicam Capsules USP, in pregnant women starting at 30 weeks of gestation (third trimester) [see Use in Specific Populations (8.1)].

5.11 Hematologic Toxicity

Anemia has occurred in NSAID-treated patients. This may be due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis. If a patient treated with Piroxicam Capsules USP has any signs or symptoms of anemia, monitor hemoglobin or hematocrit.

NSAIDs, including Piroxicam Capsules USP, may increase the risk of bleeding events. Co-morbid conditions such as coagulation disorders, concomitant use of warfarin, other anticoagulants, antiplatelet agents (e.g., aspirin), serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase this risk. Monitor these patients for signs of bleeding [see Drug Interactions (7)].

5.12 Masking of Inflammation and Fever

The pharmacological activity of Piroxicam Capsules USP in reducing inflammation, and possibly fever, may diminish the utility of diagnostic signs in detecting infections.

5.13 Laboratory Monitoring

Because serious GI bleeding, hepatotoxicity, and renal injury can occur without warning symptoms or signs, consider monitoring patients on long-term NSAID treatment with a CBC and a chemistry profile periodically [see Warnings and Precautions (5.2, 5.3, 5.6)].

5.14 Ophthalmologic Effects

Because of reports of adverse eye findings with nonsteroidal anti-inflammatory agents, it is recommended that patients who develop visual complaints during treatment with Piroxicam Capsules USP have ophthalmic evaluations.

6 ADVERSE REACTIONS

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

  • Cardiovascular Thrombotic Events [see Warnings and Precautions (5.1)]
  • GI Bleeding, Ulceration and Perforation [see Warnings and Precautions (5.2)]
  • Hepatotoxicity [see Warnings and Precautions (5.3)]
  • Hypertension [see Warnings and Precautions (5.4)]
  • Heart Failure and Edema [see Warnings and Precautions (5.5)]
  • Renal Toxicity and Hyperkalemia [see Warnings and Precautions (5.6)]
  • Anaphylactic Reactions [see Warnings and Precautions (5.7)]
  • Serious Skin Reactions [see Warnings and Precautions (5.9)]
  • Hematologic Toxicity [see Warnings and Precautions (5.11)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In patients taking Piroxicam Capsules USP or other NSAIDs, the most frequently reported adverse experiences occurring in approximately 1–10% of patients are:

Cardiovascular System: Edema

Digestive System: Anorexia, abdominal pain, constipation, diarrhea, flatulence, nausea, vomiting

Nervous System: Dizziness, headache, vertigo

Skin and Appendages: Pruritus, rash

Special Senses: Tinnitus

Additional adverse experiences reported occasionally include:

Cardiovascular System: Palpitations

Digestive System: Stomatitis

Nervous System: Drowsiness

Special Senses: Blurred vision

6.2 Postmarketing Experience

The following adverse reactions have been identified during post approval use of Piroxicam Capsules USP. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Body As a Whole: Fever, infection, sepsis, anaphylactic reactions, appetite changes, death, flu-like syndrome, pain (colic), serum sickness

Cardiovascular System: Congestive heart failure, hypertension, tachycardia, syncope, arrhythmia, exacerbation of angina, hypotension, myocardial infarction, vasculitis

Digestive System: Dyspepsia, elevated liver enzymes, gross bleeding/perforation, heartburn, ulcers (gastric/duodenal), dry mouth, esophagitis, gastritis, glossitis, hematemesis, hepatitis, jaundice, melena, rectal bleeding, eructation, liver failure and pancreatitis

Hemic and Lymphatic System: Anemia, increased bleeding time, ecchymosis, eosinophilia, epistaxis, leukopenia, purpura, petechial rash, thrombocytopenia, agranulocytosis, hemolytic anemia, aplastic anemia, lymphadenopathy, pancytopenia

Hypersensitivity: Positive ANA

Metabolic and Nutritional: Weight changes, Fluid retention, hyperglycemia, hypoglycemia

Nervous System: Anxiety, asthenia, confusion, depression, dream abnormalities, insomnia, malaise, nervousness, paresthesia, somnolence, tremors, akathisia, convulsions, coma, hallucinations, meningitis, mood alterations

Respiratory System: Asthma, dyspnea, respiratory depression, pneumonia

Skin and Appendages: Alopecia, bruising, desquamation, erythema, photosensitivity, sweat, angioedema, toxic epidermal necrosis, erythema multiforme, exfoliative dermatitis, onycholysis, Stevens Johnson Syndrome, urticaria, vesiculobullous reaction

Special Senses: Conjunctivitis, hearing impairment, swollen eyes

Urogenital System: Abnormal renal function, cystitis, dysuria, hematuria, hyperkalemia, interstitial nephritis, nephrotic syndrome, oliguria/polyuria, proteinuria, renal failure, glomerulonephritis

Reproductive system and breast disorders: Female fertility decreased

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