Piroxicam

Oral
Ankylosing spondylitis, Osteoarthritis, Rheumatoid arthritis

Topical/Cutaneous
Pain and inflammation

CYP2C9 is the primary enzyme involved in the metabolism of piroxicam to form its major inactive metabolite, 5’-hydroxy-piroxicam. Individuals who lack CYP2C9 enzyme activity, known as CYP2C9 poor metabolisers, may experience higher exposure to piroxicam and increased risk of its side effects . CYP2C9*2 and *3 are the 2 allelic variants associated with reduced enzyme activity. The *2 allele is more common in Caucasians (10-20%) than in Asian (1-3%) or African (0-6%) population while the *3 allele is less common (<10% in most populations) and extremely rare in African populations.

CYP2C9 poor metabolisers (carriers of 2 decreased function alleles e.g. *2/*2, *3/*3, *2/*3)
May consider dose reduction in patients who are known or suspected to be CYP2C9 poor metabolisers (based on genotype or previous history/experience with other CYP substrates such as warfarin, phenytoin) as they may have abnormally high plasma piroxicam levels due to its reduced metabolic clearance.

CYP2C9*2 and CYP2C9*3 are genetic polymorphisms present in individuals with reduced CYP2C9 activity. Limited data from 2 published studies indicated that individuals with heterozygous CYP2C9*1/*2 (n=9), heterozygous CYP2C9*1/*3 (n=9), and homozygous CYP2C9*3/*3 (n=1) genotypes showed 1.7-, 1.7-, and 5.3-fold higher piroxicam systemic levels, respectively, as compared with individuals with CYP2C9*1/*1 (n=17) normal metaboliser genotype following single oral dose administration. The mean elimination half-life values of piroxicam for individuals with CYP2C9*1/*3 (n=9) and CYP2C9*3/*3 (n=1) genotypes were 1.7- and 8.8-fold higher as compared with CYP2C9*1/*1 (n=17).

Should be taken with food.

Hypersensitivity (including history of asthma, bronchospasm, nasal polyps, rhinitis, angioedema, urticaria, or other allergic-type reactions) to piroxicam, aspirin or other NSAIDs. Active peptic ulcer, gastrointestinal bleeding, inflammatory bowel disease; history of gastrointestinal disorders that predispose to bleeding disorders (e.g. ulcerative colitis, Crohn’s disease, cancer, diverticulitis); history of gastrointestinal ulceration, bleeding or perforation; history of serious cutaneous allergic reactions (e.g. erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis); severe heart failure. Treatment of perioperative pain in the setting of CABG surgery. Pregnancy (3rd trimester). Concomitant use with aspirin, anticoagulants, and other NSAIDs including COX-2 inhibitors.

Patients with mild to moderate CHF, ischaemic heart disease, peripheral arterial disease, cerebrovascular disease, CV events risk factors (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking); bronchial asthma, coagulation disorders, cirrhosis, nephrotic syndrome, overt renal disease, dehydration, hypovolaemia; undergoing surgical or dental procedures. Women with conceiving difficulties, undergoing infertility treatment or on investigation of infertility. Debilitated patients. Renal and hepatic impairment. Elderly. Children (topical). Pregnancy (1st-2nd trimester) and lactation. CYP2C9 poor metabolisers.

Significant: New onset or exacerbation of hypertension, hyperkalaemia, Na and fluid retention, oedema, bronchospasm, reversible female infertility, delayed ovulation, serum sickness, haematologic effects (e.g. anaemia, decreased platelet aggregation, prolonged bleeding time). Rarely, interstitial nephritis, papillary necrosis, nephrotic syndrome, renal failure.
Blood and lymphatic system disorders: Leucopenia, eosinophilia, thrombocytopenia.
Cardiac disorders: Palpitation.
Ear and labyrinth disorders: Tinnitus.
Eye disorders: Blurred vision, eye irritation and swelling.
Gastrointestinal disorders: Nausea, vomiting, constipation, flatulence, abdominal pain, diarrhoea, dyspepsia, stomatitis.
General disorders and admin site conditions: Malaise, application site reactions (e.g. irritation, erythema, pruritus, dermatitis).
Hepatobiliary disorders: Jaundice.
Investigations: Increased LFTs, increased weight.
Metabolism and nutrition disorders: Anorexia, hyperglycaemia, hypoglycaemia.
Nervous system disorders: Headache, dizziness, somnolence, vertigo, paraesthesia.
Psychiatric disorders: Depression, insomnia, confusion, mood alterations, nervousness, hallucination.
Respiratory, thoracic and mediastinal disorders: Dyspnoea.
Skin and subcutaneous tissue disorders: Rash, pruritus, photosensitivity (topical).
Vascular disorders: Vasculitis, epistaxis.
Potentially Fatal: Gastrointestinal inflammation, ulceration, bleeding and perforation; CV thrombotic events including MI and stroke, severe hepatic reactions (e.g. fulminant hepatitis, hepatic necrosis, hepatic failure), exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylactoid reactions.

Parenteral/PO: Z (NSAIDs caused foetal ductus arteriosus premature closure, foetal renal impairment and persistent pulmonary hypertension. Avoid near term, else use lowest dose for shortest time.)

This drug may cause dizziness, drowsiness, fatigue and visual disturbances, if affected, do not drive or operate machinery. Topical: Do not apply to sites affected by open lesions, dermatoses or infection.

Monitor blood pressure during initiation and throughout therapy; occult blood loss, Hb, haematocrit, serum electrolytes, renal and hepatic function tests periodically. Perform periodic ophthalmologic exam (prolonged use).

Symptoms: Lethargy, drowsiness, nausea, vomiting, epigastric pain, low-grade fever, sinus tachycardia. Rarely, hypertension, gastrointestinal bleeding, acute renal insufficiency, respiratory depression and coma. Management: Symptomatic and supportive treatment. May consider administration of activated charcoal within 1 hour of ingestion or osmotic cathartic within 4 hours of ingestion or with large overdosage.

Increased risk of gastrointestinal ulceration or bleeding with antiplatelet agents, SSRIs, corticosteroids. May exacerbate cardiac failure, decrease GFR, and increase plasma levels of cardiac glycosides. Increased risk of nephrotoxicity with ciclosporin and tacrolimus. May interfere with the natriuretic effects of diuretics. May increase plasma levels of lithium. May antagonise the hypotensive effects of antihypertensive agents. May decrease excretion of methotrexate, leading to acute toxicity. May increase risk of convulsion with quinolones. May interfere with mifepristone mediated termination of pregnancy.
Potentially Fatal: May enhance effects of anticoagulants (e.g. warfarin). Increased risk of serious gastrointestinal events with aspirin and other NSAIDs.

May slightly delay the rate of absorption with food. Increased risk of gastrointestinal bleeding with alcohol.

May result to false-positive aldosterone/renin ratio (ARR).

Description: Piroxicam, an oxicam derivative NSAID, reversibly inhibits cyclooxygenase-1 and -2 (COX-1 and -2) enzymes thereby resulting in decreased formation of prostaglandin precursors. It has analgesic, anti-inflammatory and antipyretic properties.
Onset: Analgesia: Oral: Within 1 hour; Max effect: 3-5 hours.
Pharmacokinetics:
Absorption: Well absorbed from the gastrointestinal tract. Slightly delayed rate of absorption with food. Time to peak plasma concentration: 3-5 hours.
Distribution: Enters breast milk. Volume of distribution: 0.14 L/kg. Plasma protein binding: 99%.
Metabolism: Extensively metabolised in the liver via hydroxylation of the pyridyl ring side chain followed by conjugation with glucuronic acid.
Excretion: Via urine and faeces (<5% as unchanged drug). Elimination half-life: Approx 50 hours.

Source: National Center for Biotechnology Information. PubChem Database. Piroxicam, CID=54676228, https://pubchem.ncbi.nlm.nih.gov/compound/Piroxicam (accessed on Jan. 22, 2020)

Store between 20-25°C.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

M02AA07 - piroxicam ; Belongs to the class of non-steroidal antiinflammatory preparations for topical use. Used in the treatment of joint and muscular pains.
M01AC01 - piroxicam ; Belongs to the class of non-steroidal antiinflammatory and antirheumatic products, oxicams.

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