DailyMed Label: Feldene

DailyMed Label: Feldene

2010

DailyMed Prescription

Feldene

Piroxicam

Keltman Pharmaceuticals Inc.

NDC: 68387-700

NDC: 68387-700

Piroxicam capsules contain piroxicam which is a member of the oxicam group of non-steroidal anti-inflammatory drugs (NSAIDs). 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, 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, sodium lauryl sulfate, and titanium dioxide. piroxicam capsule

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.

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 ). After observing the response to initial therapy with piroxicam capsules, 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, 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.

Piroxicam capsules are contraindicated in patients with known hypersensitivity to piroxicam. Piroxicam capsules should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients (see WARNINGS , Anaphylactoid Reactions and PRECAUTIONS , Preexisting Asthma ). Piroxicam capsules are contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS ).

Piroxicam capsules cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids. The pharmacological activity of piroxicam capsules in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions. Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including piroxicam capsules. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continuing therapy. Notable elevations of ALT or AST (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes have been reported. A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with piroxicam capsules. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), piroxicam capsules should be discontinued (see ADVERSE REACTIONS ). Anemia is sometimes seen in patients receiving NSAIDs, including piroxicam capsules. This may be due to fluid retention, occult or gross GI blood loss, or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with NSAIDs, including piroxicam capsules, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia. NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively less, of shorter duration, and reversible. Patients receiving piroxicam capsules who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored. Because of reports of adverse eye findings with non-steroidal anti-inflammatory agents, it is recommended that patients who develop visual complaints during treatment with piroxicam capsules have ophthalmic evaluations. Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm which can be fatal. Since cross reactivity, including bronchospasm, between aspirin and other non-steroidal anti-inflammatory drugs has been reported in such aspirin-sensitive patients, piroxicam capsules should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with preexisting asthma. 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 serious 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. Because serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms of GI bleeding. Patients on long-term treatment with NSAIDs should have their CBC and a chemistry profile checked periodically. If clinical signs and symptoms consistent with liver or renal disease develop, systemic manifestations occur (e.g., eosinophilia, rash, etc.) or if abnormal liver tests persist or worsen, piroxicam capsules should be discontinued. 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. 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 capsules and aspirin is not generally recommended because of the potential for increased adverse effects. 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. 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. 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. 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. 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. Subacute, acute and chronic toxicity studies have been carried out in rats, mice, dogs, and monkeys. The pathology most often seen was that characteristically associated with the animal toxicology of anti-inflammatory agents: renal papillary necrosis (see PRECAUTIONS ) and gastrointestinal lesions. Reproductive studies revealed no impairment of fertility in animals. 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. 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. In rat studies with NSAIDs, as with other drugs known to inhibit prostaglandin synthesis, an increased incidence of dystocia, delayed parturition, and decreased pup survival occurred. The effects of piroxicam on labor and delivery in pregnant women are unknown. 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. Safety and effectiveness in pediatric patients have not been established. 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 GI 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.

In patients taking piroxicam capsules or other NSAIDs, the most frequently reported adverse experiences occurring in approximately 1 to 10% of patients are:

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. 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 capsules and aspirin is not generally recommended because of the potential for increased adverse effects. 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. 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. 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. 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. 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.

Piroxicam capsules have not been investigated in pediatric patients. Pharmacokinetic differences due to race have not been identified. The effects of hepatic disease on piroxicam pharmacokinetics have not been established. However, a substantial portion of piroxicam elimination occurs by hepatic metabolism. Consequently, patients with hepatic disease may require reduced doses of piroxicam as compared to patients with normal hepatic function. Piroxicam pharmacokinetics have been investigated in patients with renal insufficiency. Studies indicate patients with mild to moderate renal impairment may not require dosing adjustments. However, the pharmacokinetic properties of piroxicam in patients with severe renal insufficiency or those receiving hemodialysis are not known.

Piroxicam capsules USP, 20 mg are a #2 capsule with a dark green cap and a dark green body imprinted "93" "756" on the cap and body. They are available in bottles of 15. 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 for: Keltman Pharmaceuticals Inc. 1 Lakeland Square, Suite A Flowood, Ms 39232 R4

Piroxicam capsules are a non-steroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, analgesic, and antipyretic activities in animal models. The mechanism of action of piroxicam, like that of other NSAIDs, is not completely understood but may be related to prostaglandin synthetase inhibition. Piroxicam is well absorbed following oral administration. Drug plasma concentrations are proportional for 10 and 20 mg doses and generally peak within three to five hours after medication. The prolonged half-life (50 hours) results in the maintenance of relatively stable plasma concentrations throughout the day on once daily doses and to significant accumulation upon multiple dosing. A single 20 mg dose generally produces peak piroxicam plasma levels of 1.5 to 2 mcg/mL, while maximum drug plasma concentrations, after repeated daily ingestion of 20 mg piroxicam capsules, usually stabilize at 3 to 8 mcg/mL. Most patients approximate steady- state plasma levels within 7 to 12 days. Higher levels, which approximate steady state at two to three weeks, have been observed in patients in whom longer plasma half-lives of piroxicam occurred. With food there is a slight delay in the rate but not the extent of absorption following oral administration. The concomitant administration of antacids (aluminum hydroxide or aluminum hydroxide with magnesium hydroxide) have been shown to have no effect on the plasma levels of orally administered piroxicam. The apparent volume of distribution of piroxicam is approximately 0.14 L/kg. Ninety-nine percent of plasma piroxicam is bound to plasma proteins. 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. Metabolism of piroxicam occurs by hydroxylation at the 5 position of the pyridyl side chain and conjugation of this product; by cyclodehydration; and by a sequence of reactions involving hydrolysis of the amide linkage, decarboxylation, ring contraction and N -demethylation. The biotransformation products of piroxicam metabolism are reported to not have any anti-inflammatory activity. Piroxicam and its biotransformation products are excreted in urine and feces, with about twice as much appearing in the urine as in the feces. Approximately 5% of a piroxicam dose is excreted unchanged. The plasma half-life (T ½ ) for piroxicam is approximately 50 hours. Piroxicam capsules have not been investigated in pediatric patients. Pharmacokinetic differences due to race have not been identified. The effects of hepatic disease on piroxicam pharmacokinetics have not been established. However, a substantial portion of piroxicam elimination occurs by hepatic metabolism. Consequently, patients with hepatic disease may require reduced doses of piroxicam as compared to patients with normal hepatic function. Piroxicam pharmacokinetics have been investigated in patients with renal insufficiency. Studies indicate patients with mild to moderate renal impairment may not require dosing adjustments. However, the pharmacokinetic properties of piroxicam in patients with severe renal insufficiency or those receiving hemodialysis are not known. In controlled clinical trials, the effectiveness of piroxicam has been established for both acute exacerbations and long-term management of rheumatoid arthritis and osteoarthritis. The therapeutic effects of piroxicam are evident early in the treatment of both diseases with a progressive increase in response over several (8 to 12) weeks. Efficacy is seen in terms of pain relief and, when present, subsidence of inflammation. Doses of 20 mg/day piroxicam display a therapeutic effect comparable to therapeutic doses of aspirin, with a lower incidence of minor gastrointestinal effects and tinnitus. Piroxicam has been administered concomitantly with fixed doses of gold and corticosteroids. The existence of a “steroid-sparing” effect has not been adequately studied to date.

Package Label - Principal Display Panel – 15-count Bottle, 20 mg Capsules NDC 68387-700-15 Rx Only piroxicam capsule