Piroxicam 20 MG Oral Capsule
WARNINGS
Cardiovascular Effects 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, myocardial infarction, and stroke, which can be fatal.
All NSAIDs, both COX-2 selective and nonselective, may have a similar risk.
Patients with known CV disease or risk factors for CV disease may be at greater risk.
To minimize the potential risk for an adverse CV event in patients treated with an NSAID, the lowest effective dose should be used for the shortest duration possible.
Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms.
Patients should be informed about the signs and/or 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 does increase the risk of serious GI events (see , Gastrointestinal Effects – Risk of Ulceration, Bleeding, and Perforation ).
Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10 to 14 days following CABG surgery found an increased incidence of myocardial infarction and stroke (see CONTRAINDICATIONS ).
Hypertension NSAIDs, including piroxicam capsules, can lead to onset of new hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events.
Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs.
NSAIDs, including piroxicam capsules, should be used with caution in patients with hypertension.
Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.
Congestive Heart Failure and Edema Fluid retention and edema have been observed in some patients taking NSAIDs.
Piroxicam capsules should be used with caution in patients with fluid retention or heart failure.
Gastrointestinal Effects – Risk of Ulceration, Bleeding, and Perforation NSAIDs, including piroxicam capsules, can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal.
These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs.
Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic.
Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3 to 6 months, and in about 2 to 4% of patients treated for one year.
These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy.
However, even short-term therapy is not without risk.
NSAIDs should be prescribed with extreme caution in those with a prior history of ulcer disease or gastrointestinal bleeding.
Patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding who use NSAIDs have a greater than 10 fold increased risk for developing a GI bleed compared to patients with neither of these risk factors.
Other factors that increase the risk of GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status.
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 in patients treated with an NSAID, the lowest effective dose should be used for the shortest possible duration.
Patients and physicians should remain alert for signs and symptoms of GI ulcerations and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI event is suspected.
This should include discontinuation of the NSAID until a serious GI adverse event is ruled out.
For high-risk patients, alternate therapies that do not involve NSAIDs should be considered.
Renal Effects 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 a non-steroidal anti-inflammatory drug 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, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors, and the elderly.
Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
Advanced Renal Disease No information is available from controlled clinical studies regarding the use of piroxicam capsules in patients with advanced renal disease.
Therefore, treatment with piroxicam capsules is not recommended in these patients with advanced renal disease.
If piroxicam capsule therapy must be initiated, close monitoring of the patient’s renal function is advisable.
Anaphylactoid Reactions As with other NSAIDs, anaphylactoid reactions may occur in patients without known prior exposure to piroxicam capsules.
Piroxicam capsules should not be given to patients with the aspirin 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 aspirin or other NSAIDs (see CONTRAINDICATIONS and PRECAUTIONS , Preexisting Asthma ).
Emergency help should be sought in cases where an anaphylactoid reaction occurs.
Skin Reactions NSAIDs, including piroxicam capsules, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal.
These serious events may occur without warning.
Patients should be informed about the signs and symptoms of serious skin manifestations and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.
Other Hypersensitivity Reactions A combination of dermatological and/or allergic signs and symptoms suggestive of serum sickness have occasionally occurred in conjunction with the use of piroxicam.
These include arthralgias, pruritus, fever, fatigue, and rash including vesiculobullous reactions and exfoliative dermatitis.
Pregnancy In late pregnancy, as with other NSAIDs, piroxicam capsules should be avoided because it may cause premature closure of the ductus arteriosus.
DRUG INTERACTIONS
Drug Interactions Highly Protein Bound Drugs Piroxicam is highly protein bound and, therefore, might be expected to displace other protein bound drugs.
Physicians should closely monitor patients for a change in dosage requirements when administering piroxicam capsules to patients on other highly protein bound drugs.
Aspirin When piroxicam is administered with aspirin, its protein binding is reduced, although the clearance of free piroxicam is not altered.
Plasma levels of piroxicam are depressed to approximately 80% of their normal values when piroxicam is administered (20 mg/day) in conjunction with aspirin (3900 mg/day).
The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant administration of piroxicam and aspirin is not generally recommended because of the potential for increased adverse effects.
Methotrexate NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices.
This may indicate that they could enhance the toxicity of methotrexate.
Caution should be used when NSAIDs are administered concomitantly with methotrexate.
ACE-Inhibitors Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors.
This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE-inhibitors.
Diuretics Clinical studies, as well as postmarketing observations, have shown that piroxicam capsules can reduce the natriuretic effect of furosemide and thiazides in some patients.
This response has been attributed to inhibition of renal prostaglandin synthesis.
During concomitant therapy with NSAIDs, the patient should be observed closely for signs of renal failure (see WARNINGS , Renal Effects ), as well as to assure diuretic efficacy.
Lithium NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance.
The mean minimum lithium concentration increased 15% and the renal clearance was decreased by approximately 20%.
These effects have been attributed to inhibition of renal prostaglandin synthesis by the NSAID.
Thus, when NSAIDs and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity.
Warfarin The effects of warfarin and NSAIDs on GI bleeding are synergistic, such that users of both drugs together have a risk of serious GI bleeding higher than users of either drug alone.
OVERDOSAGE
Symptoms following acute NSAID overdoses are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are generally reversible with supportive care.
Gastrointestinal bleeding can occur.
Hypertension, acute renal failure, respiratory depression, and coma may occur, but are rare.
Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs, and may occur following an overdose.
Patients should be managed by symptomatic and supportive care following an NSAID overdose.
There are no specific antidotes.
Emesis and/or activated charcoal (60 to 100 g in adults, 1 to 2 g/kg in children) and/or osmotic cathartic may be indicated.
The long plasma half-life of piroxicam should be considered when treating an overdose with piroxicam.
Experiments in dogs have demonstrated that the use of multiple-dose treatments with activated charcoal could reduce the half-life of piroxicam by more than 50% and systemic bioavailability by as much as 37% when activated charcoal is given as late as 6 hours after ingestion of piroxicam.
Forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may not be useful due to high protein binding.
DESCRIPTION
Piroxicam capsules USP contain piroxicam which is a member of the oxicam group of non-steroidal anti-inflammatory drugs (NSAIDs).
Each dark green and olive capsule contains 10 mg piroxicam, each dark green capsule contains 20 mg piroxicam for oral administration.
The chemical name for piroxicam is 4-hydroxy-2-methyl- N -2-pyridinyl-2 H -1,2-benzothiazine-3-carboxamide 1,1-dioxide.
Members of the oxicam family are not carboxylic acids, but they are acidic by virtue of the enolic 4-hydroxy substituent.
Piroxicam occurs as a white crystalline solid, sparingly soluble in water, dilute acid, and most organic solvents.
It is slightly soluble in alcohol and in aqueous alkaline solutions.
It exhibits a weakly acidic 4-hydroxy proton (pKa 5.1) and a weakly basic pyridyl nitrogen (pKa 1.8).
It has the following structural formula: C 15 H 13 N 3 O 4 S M.W.
331.35 Each capsule, for oral administration, contains 10 mg or 20 mg piroxicam.
In addition, each capsule contains the following inactive ingredients: colloidal silicon dioxide, corn starch, D&C Yellow No.
10, FD&C Green No.
3, gelatin, lactose, magnesium stearate, povidone, shellac, sodium lauryl sulfate, and titanium dioxide.
The imprinting ink may contain antifoam DC 1510, 2-ethoxyethanol, lecithin, poly(dimethylsiloxane), propylene glycol, silicon dioxide, and sodium hydroxide.
Piroxicam capsules USP, 10 mg also contain: black iron oxide, FD&C Blue No.
1, and yellow iron oxide.
piroxicam structural formula
HOW SUPPLIED
Repackaged by Aphena Pharma Solutions – TN.
See Repackaging Information for available configurations.
Piroxicam capsules USP, 10 mg are a #2 capsule with a dark green cap and an olive body imprinted “93” “756” on the cap and body.
They are available in bottles of 100.
Piroxicam capsules USP, 20 mg are a #2 capsule with a dark green cap and a dark green body imprinted “93” “757” on the cap and body.
They are available in bottles of 100 and 500.
Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].
Dispense in a tight, light-resistant container as defined in the USP with a child-resistant closure (as required).
Manufactured In Israel By: TEVA PHARMACEUTICAL IND.
LTD.
Jerusalem, 91010, Israel Manufactured For: TEVA PHARMACEUTICALS USA Sellersville, PA 18960 Rev.
O 10/2011
GERIATRIC USE
Geriatric Use As with any NSAID, caution should be exercised in treating the elderly (65 years and older).
Most spontaneous reports of fatal GI events with NSAIDs are in the elderly or debilitated patients and, therefore, care should be taken in treating this population.
In addition to a past history of ulcer disease, older age and poor general health status (among other factors) may increase the risk for GI bleeding.
To minimize the potential risk of an adverse GI event, the lowest effective dose should be used for the shortest possible duration (see WARNINGS , Gastrointestinal Effects – Risk of Ulceration , Bleeding, and Perforation ).
As with all other NSAIDs, there is a risk of developing renal toxicity in patients in which renal prostaglandins have a compensatory role in maintenance of renal perfusion.
Discontinuation of non-steroidal anti-inflammatory drug therapy is usually followed by recovery to the pretreatment state (see WARNINGS , Renal Effects ).
In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting a greater frequency of impaired drug elimination and of concomitant disease or other drug therapy.
INDICATIONS AND USAGE
Carefully consider the potential benefits and risks of piroxicam capsules and other treatment options before deciding to use piroxicam capsules.
Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS ).
Piroxicam capsules are indicated: For relief of the signs and symptoms of osteoarthritis.
For relief of the signs and symptoms of rheumatoid arthritis.
PEDIATRIC USE
Pediatric Use Safety and effectiveness in pediatric patients have not been established.
PREGNANCY
Pregnancy Teratogenic Effects Pregnancy category C Reproductive studies conducted in rats and rabbits have not demonstrated evidence of developmental abnormalities.
However, animal reproduction studies are not always predictive of human response.
There are no adequate and well-controlled studies in pregnant women.
Piroxicam capsules are not recommended for use in pregnant women since safety has not been established in humans.
Piroxicam capsules should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nonteratogenic Effects Because of the known effects of non-steroidal anti-inflammatory drugs on the fetal cardiovascular system (closure of ductus arteriosus), use during pregnancy (particularly late pregnancy) should be avoided.
In animal studies of piroxicam, gastrointestinal tract toxicity was increased in pregnant females in the last trimester of pregnancy compared to nonpregnant females or females in earlier trimesters of pregnancy.
NUSRING MOTHERS
Nursing Mothers Piroxicam is excreted into human milk.
The presence in breast milk has been determined during initial and long-term conditions (52 days).
Piroxicam appeared in breast milk at about 1% to 3% of the maternal concentration.
No accumulation of piroxicam occurred in milk relative to that in plasma during treatment.
Piroxicam capsules are not recommended for use in nursing mothers.
BOXED WARNING
Cardiovascular Risk NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal.
This risk may increase with duration of use.
Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk (see WARNINGS ).
Piroxicam capsules are contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS ).
Gastrointestinal Risk NSAIDs cause an increased risk of serious gastrointestinal 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 are at greater risk for serious gastrointestinal events (see WARNINGS ).
INFORMATION FOR PATIENTS
Information for Patients Patients should be informed of the following information before initiating therapy with an NSAID and periodically during the course of ongoing therapy.
Patients should also be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed.
Piroxicam capsules, like other NSAIDs, may cause CV side effects, such as MI or stroke, which may result in hospitalization and even death.
Although serious CV events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, weakness, slurring of speech, and should ask for medical advice when observing any indicative signs or symptoms.
Patients should be apprised of the importance of this follow-up (see WARNINGS , Cardiovascular Effects ).
Piroxicam capsules, like other NSAIDs, can cause GI discomfort and, rarely, serious GI side effects, such as ulcers and bleeding, which may result in hospitalization and even death.
Although serious GI tract ulcerations and bleeding can occur without warning symptoms, patients should be alert for the signs and symptoms of ulcerations and bleeding, and should ask for medical advice when observing any indicative signs or symptoms including epigastric pain, dyspepsia, melena, and hematemesis.
Patients should be apprised of the importance of this follow-up (see WARNINGS , Gastrointestinal Effects – Risk of Ulceration , Bleeding, and Perforation ).
Piroxicam capsules, like other NSAIDs, can cause serious skin side effects such as exfoliative dermatitis, SJS and TEN, which may result in hospitalization and even death.
Although serious skin reactions may occur without warning, patients should be alert for the signs and symptoms of skin rash and blisters, fever, or other signs of hypersensitivity such as itching, and should ask for medical advice when observing any indicative signs or symptoms.
Patients should be advised to stop the drug immediately if they develop any type of rash and contact their physicians as soon as possible.
Patients should promptly report signs or symptoms of unexplained weight gain or edema to their physicians.
Patients should be informed of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and “flu-like” symptoms).
If these occur, patients should be instructed to stop therapy and seek immediate medical therapy.
Patients should be informed of the signs of an anaphylactoid reaction (e.g., difficulty breathing, swelling of the face or throat).
If these occur, patients should be instructed to seek immediate emergency help (see WARNINGS ).
In late pregnancy, as with other NSAIDs, piroxicam capsules should be avoided because they may cause premature closure of the ductus arteriosus.
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 dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS ).
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 recommended dose 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 to 12 days.
Therefore, although the therapeutic effects of piroxicam 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.