Piroxicam (Piroxicam) - Description and Clinical Pharmacology

Rx only

DESCRIPTION

Piroxicam Capsules, USP contain piroxicam which is a member of the oxicam group of non-steroidal anti-inflammatory drugs (NSAIDs). Each light green and bright orange capsule contains 10 mg piroxicam, each green capsule contains 20 mg piroxicam for oral administration. The chemical name for piroxicam is 4-hydroxyl-2-methyl- N -2-pyridinyl-2 H -1,2,-benzothiazine-3-carboxamide 1,1-dioxide. 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 solutions. It exhibits a weakly acidic 4-hydroxy proton (pKa 5.1) and a weakly basic pyridyl nitrogen (pKa 1.8). The molecular weight of piroxicam is 331.35. Its molecular formula is C₁₅H₁₃N₃O₄S and it has the following structural formula:

The inactive ingredients in piroxicam capsules include: colloidal silicon dioxide, gelatin, lactose (hydrous), magnesium stearate, microcrystalline cellulose, polyethylene glycol, sodium lauryl sulfate and titanium dioxide. The capsules contain the following coloring agents:

•  10 mg - FD&C Blue No. 1, Black Iron Oxide, Yellow Iron Oxide, FD&C Green
•  No. 3, D&C Yellow No. 10.
•  20 mg - FD&C Green No. 3, D&C Yellow No. 10, FD&C Yellow No. 6.

CLINICAL PHARMACOLOGY

Pharmacodynamics

Piroxicam is 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.

Pharmacokinetics

Absorption

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, 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.

Distribution

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

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.

Excretion

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_1/2) for piroxicam is approximately 50 hours.

Special Populations

Pediatric

Piroxicam has not been investigated in pediatric patients.

Race

Pharmacokinetic differences due to race have not been identified.

Hepatic Insufficiency

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.

Renal Insufficiency

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.

Other Information

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.