Tenoxicam

Tenoxicam is Non- Steroidal Ant inflammatory Drugs belonging to Analgesic and Anti inflammatory agents.

Tenoxicam is used in the treatment of ankylosing spondylitis, extra-articular inflammation, osteoarthritis, rheumatoid arthritis.

Tenoxicam is Well absorbed from the GI tract and get rapidly absorbed after IM inj. Food may delay the rate (to approx 6 hr) of absorption and penetrates synovial fluid. Plasma protein binding: Approx 99% and get completely metabolised to inactive metabolites and get Mainly excreted via urine, some via bile as glucoronide conjugates of the metabolites. Plasma elimination half-life: 42-81 hr.

The onset of action of Tenoxicam was within 1 hour.

The Tmax of Tenoxicam was within 0.5-6 hours.

Tenoxicam shows common side effects like Dyspepsia, nausea, abdominal pain and discomfort, constipation, diarrhea, flatulence, indigestion, epigastric distress, stomatitis, anorexia; peripheral oedema; headache, dizziness.

Tenoxicam is an NSAID which has marked anti-inflammatory and analgesic activity and some antipyretic activity. As w/ other NSAIDs, the precise mode of action is unknown, though it is probably multifactorial, involving inhibition of prostaglandin biosynthesis and reduction of leucocyte accumulation at the inflammatory site.

Tenoxicam is available in the form of Tablets.

Tenoxicam is used in the treatment of ankylosing spondylitis, extra-articular inflammation, osteoarthritis, rheumatoid arthritis.

Tenoxicam is approved for use in the following clinical indications

Ankylosing spondylitis: Symptomatic treatment of ankylosing spondylitis

Extra-articular inflammation: Symptomatic treatment of extra-articular inflammation (eg tendinopathy, bursitis and periarthritis of the shoulders or hips)

Osteoarthritis: Symptomatic treatment of osteoarthritis (OA)

Rheumatoid arthritis: Symptomatic treatment of rheumatoid arthritis (RA).

Tenoxicam is available in the dosage strength of 20 mg.

Tenoxicam is available in the form of Tablet.

Dosage Adjustment in Kidney Patient

• eGFR 30 to <60 mL/minute/1.73 m²: Temporarily discontinue in patients with intercurrent disease that increases risk of acute kidney injury.
• eGFR <30 mL/minute/1.73 m²: Avoid use.

Dosage Adjustment in Hepatic impairment Patient

• Hepatic impairment prior to treatment initiation:
• There are no specific dosage adjustments provided in the manufacturer’s labeling; however, a dosage reduction is recommended.
• Hepatotoxicity during treatment.
• Discontinue treatment if clinical signs and symptoms consistent with liver disease develop or if systemic manifestations occur.

Tenoxicam is contraindicated in patients with:

Hypersensitivity to tenoxicam or any component of the formulation; patients who have experienced asthma, urticaria, rhinitis or other allergic-type reactions after taking aspirin or other NSAIDs; active peptic ulcer or active GI inflammatory diseases; preoperative/preanesthetic use in the elderly or in patients at increased risk of renal failure or increased risk of bleeding; third trimester of pregnancy.

Concerns related to adverse effects:

• Anaphylactoid reactions: Even in patients without prior exposure anaphylactoid reactions may occur; patients with "aspirin triad" (bronchial asthma, aspirin intolerance, rhinitis) may be at increased risk. Do not use in patients who experience bronchospasm, asthma, rhinitis, or urticaria with nonsteroidal anti-inflammatory drug (NSAID) or aspirin therapy.

• Cardiovascular events: NSAIDs cause an increased risk of serious (and potentially fatal) adverse cardiovascular thrombotic events, including myocardial infarction (MI) and stroke. Risk may occur early during treatment and may increase with duration of use. Relative risk appears to be similar in those with and without known cardiovascular disease or risk factors for cardiovascular disease; however, absolute incidence of serious cardiovascular thrombotic events (which may occur early during treatment) was higher in patients with known cardiovascular disease or risk factors and in those receiving higher doses. Use caution in patients with hypertension or conditions predisposing to fluid retention. Avoid use in heart failure (FDA 2015). Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of cardiovascular events; alternate therapies should be considered for patients at high risk.

• CNS effects: NSAIDs may cause drowsiness, dizziness, blurred vision, and other neurologic effects that may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

• Drug reaction with eosinophilia and systemic symptoms: Potentially serious, sometimes fatal, drug reaction with eosinophilia and systemic symptoms (DRESS), also known as multiorgan hypersensitivity reactions, has been reported with NSAIDs. Monitor for signs and symptoms (eg, fever, rash, lymphadenopathy, eosinophilia) in association with other organ system involvement (eg, hepatitis, nephritis, hematological abnormalities, myocarditis, myositis). Early symptoms of hypersensitivity reaction (eg, lymphadenopathy, fever) may occur without rash; discontinue therapy and further evaluate if DRESS is suspected.

• GI events: Use is contraindicated in patients with active peptic ulcer or active GI inflammatory disease. Use caution in patients with a history of GI disease (bleeding or ulcers, melena, ulcerative colitis, Crohn disease), concurrent therapy with aspirin, anticoagulants and/or corticosteroids, smoking, use of alcohol, the elderly or debilitated patients. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of GI adverse events; alternate therapies should be considered for patients at high risk. When used concomitantly with aspirin, a substantial increase in the risk of GI complications (eg, ulcer) occurs; concomitant gastroprotective therapy (eg, proton pump inhibitors) is recommended.

• Hematologic effects: Platelet adhesion and aggregation may be decreased; may prolong bleeding time; patients with coagulation disorders or who are receiving anticoagulants should be monitored closely. Anemia may occur; patients on long-term NSAID therapy should be monitored for anemia. Rarely, NSAID use has been associated with potentially severe blood dyscrasias (eg, agranulocytosis, thrombocytopenia, aplastic anemia).

• Hepatic effects: Transaminase elevations have been reported with use; closely monitor patients with any abnormal liver function test. Rare (sometimes fatal) severe reactions (eg, hepatitis, jaundice, hepatic failure) have occurred with NSAID use. Discontinue immediately if signs or symptoms of hepatic disease develop or if systemic manifestations occur.

• Hyperkalemia: NSAID use may increase the risk of hyperkalemia, particularly in the elderly, diabetics, renal disease, and with concomitant use of other agents capable of inducing hyperkalemia (eg, angiotensin-converting enzyme inhibitors, beta-blockers, some diuretics). Monitor potassium closely.

• Ophthalmic events: Blurred/diminished vision has been reported; discontinue therapy and refer for ophthalmologic evaluation if symptoms occur.

• Renal effects: NSAID use may compromise existing renal function; dose-dependent decreases in prostaglandin synthesis may result from NSAID use, reducing renal blood flow, which may cause renal decompensation. Patients with impaired renal function, dehydration, hypovolemia, heart failure, hepatic impairment, those taking diuretics and ACE inhibitors, and patients ≥65 years of age are at greater risk of renal toxicity. Rehydrate patient before starting therapy. Long-term NSAID use may result in renal papillary necrosis and other renal injury.

• Skin reactions: NSAIDs may cause potentially fatal serious skin adverse events, including erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis; may occur without warning; discontinue use at first sign of skin rash (or any other hypersensitivity).

Tenoxicam may cause liver problems, and using it with substantial quantities of ethanol may increase that risk.

Pregnancy Category C

Risk Summary

Use of NSAIDs, including Tenoxicam, during the third trimester of pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Avoid use of NSAIDs, including Tenoxicam, in pregnant women starting at 30 weeks of gestation (third trimester). There are no adequate and well-controlled studies of Tenoxicam in pregnant women. Data from observational studies regarding potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive. In the general U.S. population, all clinically recognized pregnancies, regardless of drug exposure, have a background rate of 2-4% for major malformations, and 15-20% for pregnancy loss. In animal reproduction studies in rats and rabbits, there was no evidence of teratogenicity at exposures up to 5 and 10 times the MRHD, respectively. In rat studies with Tenoxicam, fetotoxicity (postimplantation loss) was observed at exposures 2 times the MRHD, and delayed parturition and an increased incidence of stillbirth were noted at doses equivalent to the MRHD of Tenoxicam. Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, administration of prostaglandin synthesis inhibitors such as Tenoxicam, resulted in increased pre- and post-implantation loss.

Increased risk of gastrointestinal bleeding with excessive alcohol ingestion. May slightly delay the rate, but not the extent of absorption with food.

• Common Adverse effects

Dyspepsia, nausea, abdominal pain and discomfort, constipation, diarrhea, flatulence, indigestion, epigastric distress, stomatitis, anorexia; peripheral oedema; headache, dizziness.

• Less Common Adverse effects

Allergic reactions, asthma, bronchospasm, dyspnea, rash, pruritus; decreased Hb, anemia, thrombocytopenia, non-thrombocytopenic purpura, leucopenia, eosinophilia, epistaxis

• Rare Adverse effects

Increased serum transaminase levels; swollen eyes, blurred vision, eye irritation, malaise, tinnitus; oedema, HTN, cardiac failure.

Increased risk of gastrointestinal ulceration or bleeding with oral corticosteroids, SSRIs, or antiplatelet agents (e.g. low-dose aspirin). May enhance the nephrotoxic effect of ciclosporin and tacrolimus. May reduce the efficacy of diuretics and antihypertensive agents (e.g. ACE inhibitors, β-blockers, ARBs). May increase plasma levels of lithium, methotrexate, and digoxin. May increase the 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.

The common side effects of Tenoxicam include the following :

Dyspepsia, nausea, abdominal pain and discomfort, constipation, diarrhoea, flatulence, indigestion, epigastric distress, stomatitits, anorexia; peripheral oedema; headache, dizziness.

Symptoms: Lethargy, nausea, vomiting, epigastric pain, drowsiness, gastrointestinal bleeding. Rarely, hypertension, acute renal failure, respiratory depression, and coma.

Management: Symptomatic and supportive treatment. Consider inducing emesis and/or administering activated charcoal (60-100 g in adults and 1-2 g/kg in children) and/or osmotic cathartic in symptomatic patients within 4 hours of ingestion or during a large overdose (5-10 times the usual dosage). Gastric lavage may also be performed if appropriate.

• Pharmacodynamic

Tenoxicam is an NSAID which has marked anti-inflammatory and analgesic activity and some antipyretic activity. As w/ other NSAIDs, the precise mode of action is unknown, though it is probably multifactorial, involving inhibition of prostaglandin biosynthesis and reduction of leucocyte accumulation at the inflammatory site.

• Pharmacokinetics

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1364710/
2. https://reference.medscape.com/drug/colestid-Tenoxicam -342452
3. https://go.drugbank.com/drugs/DB00375
4. https://www.sciencedirect.com/topics/medicine-and-dentistry/Tenoxicam
5. https://europepmc.org/article/med/6988203