Piroxicam (piroxicam)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Piroxicam is a prototypical nonsteroidal anti-inflammatory agent (NSAIA) that exhibits analgesic and antipyretic activity.
Piroxicam has pharmacologic actions similar to those of other prototypical NSAIAs. The drug exhibits anti-inflammatory, analgesic, and antipyretic activity. The exact mechanisms have not been clearly established, but many of the actions appear to be associated principally with the inhibition of prostaglandin synthesis.
Piroxicam inhibits the synthesis of prostaglandins in body tissues by inhibiting cyclooxygenase; at least 2 isoenzymes, cyclooxygenase-1 (COX-1) and -2 (COX-2) (also referred to as prostaglandin G/H synthase-1 (PGHS-1) and -2 (PGHS-2), respectively), have been identified that catalyze the formation of prostaglandins in the arachidonic acid pathway. Piroxicam, like other prototypical NSAIAs, inhibits both COX-1 and COX-2. Although the exact mechanisms have not been clearly established, NSAIAs appear to exert anti-inflammatory, analgesic, and antipyretic activity principally through inhibition of the COX-2 isoenzyme; COX-1 inhibition presumably is responsible for the drugs' unwanted effects on GI mucosa and platelet aggregation.
Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models and are mediators of inflammation. Because piroxicam is an inhibitor of prostaglandin synthesis, its mode of action may also be due to a decrease of prostaglandin in peripheral tissues. Although the mechanism of the antipyretic effect of NSAIAs is not known, it has been suggested that suppression of prostaglandin synthesis in the CNS (probably in the hypothalamus) may be involved.
Piroxicam is well absorbed following oral administration. Food decreases the rate but not the extent of absorption of piroxicam. Following oral administration of a single 20-mg dose of piroxicam, the drug appears in plasma within 15-30 minutes and peak plasma concentrations usually are reached within 3-5 hours.
In one study, the presence of a secondary peak in plasma piroxicam concentrations was reported, suggesting that piroxicam may undergo enterohepatic circulation. Relatively stable plasma concentrations of piroxicam are maintained during the day following administration of single daily doses. Following repeated daily administration of piroxicam, substantial drug accumulation occurs.
Steady-state plasma concentrations of piroxicam are usually reached within 7-12 days. Piroxicam is 99.3% bound to plasma proteins in vitro. Piroxicam is distributed into synovial fluid in concentrations about 40% of simultaneous plasma concentrations; however, substantial interindividual variation has been observed.
In addition, there is some evidence that piroxicam accumulates slowly in cartilage. Following oral administration, piroxicam is distributed into milk in concentrations approximately 1-3% of concurrent maternal plasma concentrations. The plasma half-life of piroxicam has been reported to range from 14-158 hours in healthy adults.
The manufacturer states that the half-life of piroxicam averages 50 hours.
Piroxicam appears to be extensively metabolized. The drug is metabolized principally by cytochrome P-450 isoenzyme 2C9 (CYP2C9)-mediated hydroxylation at the 5-position of the pyridinyl side chain followed by conjugation with glucuronic acid. At steady-state, about 50% of a dose of piroxicam is metabolized via hydroxylation and glucuronide conjugation of the hydroxy metabolite.
Although the rate of formation of the hydroxy metabolite is slow, the metabolite appears to be excreted and/or conjugated rapidly since only trace amounts appear in plasma. The metabolites of piroxicam reportedly do not inhibit prostaglandin synthesis and have little or no anti-inflammatory activity. In patients with the CYP2C9 poor metabolizer phenotype, metabolic clearance of piroxicam may be decreased substantially and plasma concentrations may be increased.
Metabolism may be moderately or mildly decreased in patients with the CYP2C9 intermediate metabolizer phenotype with a diplotype activity score of 1 or 1.5, respectively. Limited data indicate that piroxicam concentrations following a single oral dose are 1.7-fold higher in individuals with the heterozygous *1/*2 or *1/*3 diplotype and 5.3-fold higher in individuals with the homozygous *3/*3 diplotype, compared with normal metabolizers. The mean elimination half-life was increased 1.7-fold in those with the *1/*3 diplotype and 8.8-fold in those with the 3/*3 diplotype.
Piroxicam and its metabolites are excreted principally in urine and feces; urinary excretion of the drug is about twice the fecal excretion. Piroxicam is excreted principally as metabolites and less than 5% of an administered dose is excreted unchanged in urine and feces. Pharmacokinetic differences due to race have not been identified.
Piroxicam is used for its anti-inflammatory and analgesic effects in the symptomatic treatment of rheumatoid arthritis, osteoarthritis, and other inflammatory or painful conditions in adults.
Generic name: piroxicam
Pronunciation: (pir-OX-i-kam)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Piroxicam
Indications
The following indications are listed for Piroxicam:
- Osteoarthritis
- Rheumatoid Arthritis
Also known as: Arthritis Deformans, Arthrosis Deformans, Degenerative Arthritis, Degenerative Joint Disease, Degenerative Polyarthritis, Hypertrophic Arthritis, Nodose Rheumatism, Osteoarthrosis, Rheumatic Arthritis, Rheumatic Gout.
Dosing
The lowest possible effective dosage and shortest duration of therapy consistent with treatment goals of the patient should be used. Dosage of piroxicam must be adjusted carefully according to individual requirements and response.
Piroxicam is administered orally.
Piroxicam is usually administered as a single daily dose but may be administered in divided doses daily.
Store piroxicam capsules in a tight, light-resistant container at 20-25degreesC.
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No dosing information is available for this tab.
Drug interactions
Piroxicam is metabolized primarily by cytochrome P-450 (CYP) 2C9.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to piroxicam or any ingredient in the formulation.
*History of asthma, urticaria, or other sensitivity reaction precipitated by aspirin or other nonsteroidal anti-inflammatory agents (NSAIAs).
*In the setting of coronary artery bypass graft (CABG) surgery.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
The most common adverse effects of piroxicam (>=2% of patients) reported in clinical trials were nausea, constipation, flatulence, abdominal pain, diarrhea, headache, dizziness, edema, and rash.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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Safety and efficacy of piroxicam have not been established in pediatric patients.
Use of NSAIAs during pregnancy at about 30 weeks of gestation or later can cause premature closure of the fetal ductus arteriosus, and use at about 20 weeks of gestation or later has been associated with fetal renal dysfunction resulting in oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, use of NSAIAs should be avoided in pregnant women at about 30 weeks of gestation or later; if NSAIA therapy is necessary between about 20 and 30 weeks of gestation, the lowest effective dosage and shortest possible duration of treatment should be used. Monitoring of amniotic fluid volume via ultrasound examination should be considered if the duration of NSAIA treatment exceeds 48 hours; if oligohydramnios occurs, the drug should be discontinued and follow-up instituted according to clinical practice.
Fetal renal dysfunction resulting in oligohydramnios and, in some cases, neonatal renal impairment has been observed, on average, following days to weeks of maternal NSAIA use, although oligohydramnios has been observed infrequently as early as 48 hours after initiation of NSAIA therapy. Oligohydramnios is often, but not always, reversible (generally within 3-6 days) following discontinuance of NSAIA therapy. Complications of prolonged oligohydramnios may include limb contracture and delayed lung maturation. A limited number of case reports have described maternal NSAIA use and neonatal renal dysfunction, in some cases irreversible, without oligohydramnios. Some cases of neonatal renal dysfunction have required treatment with invasive procedures such as exchange transfusion or dialysis. Deaths associated with neonatal renal failure have been reported.
Animal data indicate that prostaglandins have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, inhibitors of prostaglandin synthesis, such as piroxicam, were associated with increased pre- and post-implantation losses. Prostaglandins also have an important role in fetal kidney development. In animal studies, inhibitors of prostaglandin synthesis impaired kidney development at clinically relevant doses.
Animal reproduction studies in rats and rabbits receiving piroxicam revealed no evidence of teratogenicity at exposures up to 5 and 10 times, respectively, the maximum recommended human dose (MRHD). In rats, fetotoxicity (post-implantation loss) was observed at exposure levels of twice the MRHD, and delayed parturition and an increased incidence of stillbirth were observed at doses equivalent to the MRHD.
Data are lacking on the effects of piroxicam during labor or delivery. In animal studies, NSAIAs, including piroxicam, inhibited prostaglandin synthesis, delayed parturition, and increased the incidence of stillbirth.
Limited data indicate that piroxicam is distributed into human milk at concentrations of approximately 1-3% of the maternal concentration. No accumulation of the drug in milk relative to maternal plasma was observed. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for piroxicam and any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.
The manufacturer recommends initiating piroxicam at the lowest effective dosage for the shortest possible duration with close monitoring for adverse effects.
Geriatric patients are at greater risk for NSAIA-associated serious cardiovascular, GI, and/or renal adverse events compared to younger patients. Geriatric individuals appear to tolerate GI ulceration and bleeding less well than other individuals, and most spontaneous reports of fatal GI effects occur in such patients. If the anticipated benefits outweigh the potential risks of therapy, use the lowest effective dosage of piroxicam for the shortest possible duration and monitor for adverse effects.
ICD codes
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Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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