Meloxicam

Oral
Ankylosing spondylitis
Adult: For the long-term symptomatic treatment of cases: 15 mg once daily, may decrease to 7.5 mg once daily as necessary. Use the lowest effective dose for the shortest possible duration.
Child: ≥16 years Same as adult dose.
Elderly: 7.5 mg daily.
Renal impairment: Patient on dialysis: As tab and oral susp: Max: 7.5 mg daily.
Hepatic impairment: Severe: Contraindicated.

Oral
Rheumatoid arthritis
Adult: For the long-term symptomatic treatment of cases: 15 mg once daily, may decrease to 7.5 mg once daily as necessary. Use the lowest effective dose for the shortest possible duration.
Child: ≥16 years Same as adult dose.
Elderly: 7.5 mg daily.
Renal impairment: Patient on dialysis: As tab and oral susp: Max: 7.5 mg daily.
Hepatic impairment: Severe: Contraindicated.

Oral
Osteoarthritis
Adult: For the short-term symptomatic treatment of acute exacerbations: As tab and oral susp: 7.5 mg once daily, may increase to 15 mg once daily if necessary. As cap: 5 mg once daily, may increase up to 10 mg daily as necessary. Use the lowest effective dose for the shortest possible duration.
Child: ≥16 years Same as adult dose.
Renal impairment: Patient on dialysis: As tab and oral susp: Max: 7.5 mg daily. As cap: Max: 5 mg daily.
Hepatic impairment: Severe: Contraindicated.

Oral
Juvenile idiopathic arthritis
Child: For the treatment of the signs and symptoms of pauciarticular or polyarticular course: ≥2 years weighing ≥60 kg: As tab: 7.5 mg once daily. As oral susp: 0.125 mg/kg once daily. Max: 7.5 mg once daily. Use the lowest effective dose for the shortest possible duration. Treatment recommendations may vary among countries and individual products (refer to specific product guidelines).
Renal impairment: Patient on dialysis: As tab and oral susp: Max: 7.5 mg daily.
Hepatic impairment: Severe: Contraindicated.

Intravenous
Mild to moderate pain
Adult: As monotherapy or in combination with non-NSAID analgesics: 30 mg once daily via IV bolus inj over 15 seconds. Use for the shortest duration consistent with the patient's treatment goals.
Hepatic impairment: Severe: Contraindicated.

Special Populations: Pha rmacogenomics: Meloxicam is metabolised by the CYP2C9 hepatic enzyme. Genetic polymorphism of the CYP2C9 gene may affect meloxicam metabolism thereby causing sustained elevations in drug exposure. Although available product information may not reference pharmacogenomic information, CYP2C9 genotyping test may be considered prior to treatment initiation (particularly during IV use). Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline as of March 2020: CYP2C9 intermediate metaboliser (activity score of 1.5) Patients carrying 1 normal functional allele and 1 decreased functional allele (e.g. *1/*2). These patients exhibit a mildly reduced metabolism of meloxicam. Initiate therapy with recommended starting dose. Use the lowest effective dose for the shortest possible duration consistent with the patient's treatment goals. CYP2C9 intermediate metaboliser (activity score of 1) Patients carrying 1 normal functional allele and 1 non-functional allele; or 2 decreased functional allele (e.g. *1/*3, *2/*2). These patients exhibit a moderately reduced metabolism of meloxicam. Initially, administer 50% of the lowest recommended starting dose, titrate doses upward to clinical effect or until 50% of the Max recommended dose is given (initiate upward titration after steady-state is attained). Use the lowest effective dose for the shortest possible duration consistent with the patient's treatment goals. Alternatively, consider other agents that are not metabolised by CYP2C9 or not significantly affected by CYP2C9 genetic variants in vivo or an NSAID metabolised by CYP2C9 but with a shorter half-life. CYP2C9 poor metaboliser (activity score of 0 or 0.5) Patients carrying 1 non-functional allele and 1 decreased functional allele; or 2 non-functional alleles (e.g. *2/*3,*3/*3). These patients exhibit significantly reduced metabolism and prolonged meloxicam half-life; increased risk and severity of toxicities with higher plasma concentrations. Consider other agents that are not metabolised by CYP2C9 or not significantly affected by CYP2C9 genetic variants in vivo or an NSAID metabolised by CYP2C9 but with a shorter half-life.

May be taken with or without food. May be taken w/ meals if GI discomfort occurs.

Hypersensitivity; history of asthma, urticaria, or allergic-type reactions after aspirin or other NSAID use. Active or history of recurrent peptic ulceration or bleeding (≥2 distinct episodes of proven ulceration or bleeding), history of cerebrovascular bleeding or other bleeding disorders; history of gastrointestinal bleeding or perforation associated with previous NSAID therapy; severe heart failure; active intestinal inflammatory disease (e.g. Crohn's disease, ulcerative colitis). Phenylketonuria (orally disintegrating tab). Moderate to severe renally impaired patient who are at risk for renal failure due to volume depletion (IV). Use in the setting of CABG surgery. Severe hepatic and renal (non-dialysed) impairment. Pregnancy (3rd trimester).

Patient with a history of ulcerative colitis or Crohn's disease; oedema, hypovolaemia, other forms of asthma, hypertension, CHF, established ischaemic heart disease, peripheral arterial disease, cerebrovascular disease, gastrointestinal disease, diabetes, coagulopathy, recent MI. Meloxicam is available in multiple formulations, certain products or formulations may only be used for certain indications and some may not be bioequivalent; refer to specific product guidelines prior to administration and do not switch between brands or formulations. Avoid chronic use after bariatric surgery; defer use for at least 4-6 half-lives before surgical or dental procedures. Not indicated for use in patients requiring relief from acute pain or when rapid onset of analgesia is required. CYP2C9 genetic polymorphism; available product information may not reference pharmacogenomic information, refer to specific country guidelines for their respective recommendations. Use may mask the usual signs and symptoms of infection. Avoid concomitant use with other NSAIDs (including cyclooxygenase-2 inhibitors). Not recommended in women undergoing investigation of infertility or having difficulty conceiving. Smokers. Dehydrated and debilitated patient. Children and elderly. Mild to moderate renal and hepatic impairment. Pregnancy (1st and 2nd trimester) and lactation. Patient Counselling This drug may cause drowsiness, dizziness, and blurred vision; if affected, do not drive or operate machinery. Monitoring Parameters Assess cardiac risk and potential for gastrointestinal bleeding prior to initiation of therapy. Monitor blood pressure, gastrointestinal effects, and ototoxicity at the start of therapy and periodically throughout use; CBC, chemistry profile, occult blood loss, periodic LFTs, renal function (e.g. urine output, serum BUN and creatinine), K level. Perform ophthalmic evaluations periodically during prolonged use. Assess for signs and symptoms of gastrointestinal bleeding. Monitor analgesic response after treatment initiation (IV).

Significant: Anaphylactoid reactions, new-onset or exacerbation of hypertension, oedema, Na and fluid retention, cardiac failure; decreased platelet adhesion and aggregation, prolonged bleeding time, increased risk of haemorrhage; anaemia (particularly with long term use); transaminase elevations (mild and transient), hyperkalaemia; blurred or decreased vision; interstitial nephritis (with or without nephrotic syndrome), impaired renal function, renal papillary necrosis; anastomotic ulcerations/perforations (if used after bariatric surgery). Rarely, severe blood dyscrasias (e.g. agranulocytosis, thrombocytopenia, aplastic anaemia). Ear and labyrinth disorders: Vertigo. Gastrointestinal disorders: Nausea, vomiting, diarrhoea, dyspepsia, abdominal pain, constipation, flatulence, stomatitis, gastritis, eructation, exacerbation of colitis and Crohn's disease. Investigations: Abnormal renal function test (e.g. increased serum creatinine and/or serum urea). Nervous system disorders: Headache, dizziness, somnolence. Skin and subcutaneous tissue disorders: Rash, pruritus, angioedema. Vascular disorders: Flushing.
Potentially Fatal: CV thrombotic events including MI and stroke (increased risk with higher doses and prolonged use); gastrointestinal bleeding, ulceration, and perforation; drug reaction with eosinophilia and systemic symptoms (DRESS)/multiorgan hypersensitivity, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis. Rarely, severe hepatic reactions (e.g. fulminant hepatitis, hepatic necrosis, hepatic failure).

Symptoms: Drowsiness, lethargy, nausea, vomiting, epigastric pain, gastrointestinal bleeding; convulsions, hypertension, CV collapse, cardiac arrest, acute renal failure, hepatic dysfunction, respiratory depression, coma; anaphylactic reactions. Management: Symptomatic and supportive treatment. Consider emesis or administering activated charcoal and/or osmotic cathartic in symptomatic patients seen within 4 hours of ingestion or in large overdoses. May give colestyramine to increase clearance.

Increased risk of gastrointestinal ulcers and bleeding with other NSAIDs, aspirin (at anti-inflammatory doses), other salicylates (e.g. diflunisal, salsalate), or corticosteroids. Increased risk of gastrointestinal bleeding with SSRIs. Increased risk of bleeding with anticoagulants (e.g. warfarin, heparin), thrombolytics, and antiplatelet drugs. May reduce the therapeutic effect of diuretics, β-blockers, ACE inhibitors, angiotensin receptor blockers, and intrauterine devices. Increased nephrotoxic effect of calcineurin inhibitors (e.g. ciclosporin, tacrolimus). May decrease renal excretion and increase the risk of lithium toxicity. Increased plasma concentration of methotrexate. Colestyramine increases the clearance and decreases the half-life of meloxicam. May increase the risk of myelotoxicity, nephrotoxicity, and gastrointestinal toxicity with pemetrexed. May increase the serum concentration and prolong the half-life of digoxin.

Increased risk of gastrointestinal bleeding with alcohol.

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

Meloxicam is an NSAID belonging to the oxicam family and it possesses antipyretic, analgesic, and anti-inflammatory properties. Its mechanism of action remains unknown, but it is said to involve the reversible inhibition of cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, thereby causing a reduced biosynthesis of prostaglandins.
Absorption: Well absorbed from the gastrointestinal tract. Bioavailability: 89% (tab, cap, oral susp). Time to peak plasma concentration: Oral: Initial: 4-5 hours (tab); within 2 hours (cap); 4-12 hours (orally disintegrating tab). Secondary: 12-14 hours (tab); approx 8 hours (cap). IV: 0.12 ± 0.04 hours.
Distribution: Penetrates the synovial fluid and RBC. Plasma protein binding: Approx 99.4% particularly to albumin. Volume of distribution: Oral: 11 L. IV: 9.63 L.
Metabolism: Extensively metabolised in the liver via oxidation by the CYP2C9 and to a lesser extent by CYP3A4 isoenzymes to form 4 inactive metabolites.
Excretion: Via urine (mainly as inactive metabolites; <1% as meloxicam); faeces (mainly as inactive metabolites; <5% as meloxicam). Elimination half-life: Oral: Approx 15-22 hours. IV: Approx 24 hours.

Intravenous: IV: Store between 4-30°C. Do not freeze. Protect from light. Storage instructions may vary among countries and individual products. Refer to specific product guidelines. Oral: Oral: Store below 30°C. Protect from moisture (cap). Storage instructions may vary among countries and individual products. Refer to specific product guidelines.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

M01AC06 - meloxicam ; Belongs to the class of non-steroidal antiinflammatory and antirheumatic products, oxicams.