MELOXICAM

1. Drug Name

• Generic Name: Meloxicam

• Brand Names: Mobic, Metacam, Movalis, Anjeso

2. Drug Classification

• Class: Nonsteroidal Anti-Inflammatory Drug (NSAID)

• Subclass: Oxicam derivative

3. Mechanism of Action

• Meloxicam selectively inhibits the cyclooxygenase-2 (COX-2) enzyme more than COX-1, particularly at lower doses. This selective COX-2 inhibition decreases the formation of prostaglandins responsible for pain, inflammation, and fever while minimally affecting COX-1, which is linked to gastrointestinal (GI) side effects.

• At higher doses, meloxicam may inhibit both COX-1 and COX-2, increasing the risk of GI and renal side effects.

4. Pharmacokinetics

• Absorption: Well absorbed with peak plasma concentration reached in 4-5 hours after oral dosing; bioavailability is approximately 89%.

• Distribution: Volume of distribution (Vd) is 0.1 L/kg; about 99% bound to plasma proteins.

• Metabolism: Primarily metabolized in the liver by CYP2C9 and CYP3A4 enzymes, leading to inactive metabolites.

• Excretion: Half-life (t½) is around 15-20 hours, allowing for once-daily dosing; excreted primarily via urine and feces.

• Special Considerations: The half-life may be prolonged in elderly patients, so dose adjustments may be needed.

5. Indications

• Primary Indications:

  • Osteoarthritis and rheumatoid arthritis, particularly in cases where long-term NSAID therapy is required.

  • Ankylosing spondylitis.

• Off-Label Uses:

  • Management of acute musculoskeletal pain.

• Specific Populations: Primarily indicated for adult use, though it can be used in children above the age of two years for specific conditions such as juvenile rheumatoid arthritis.

6. Dosage and Administration

• Adults:

  • Osteoarthritis: 7.5 mg once daily, may be increased to a maximum of 15 mg daily if necessary.

  • Rheumatoid Arthritis: 7.5 mg once daily, with an option to increase to 15 mg daily.

• Pediatric:

  • Juvenile Rheumatoid Arthritis (for children ≥2 years): 0.125 mg/kg once daily, up to a maximum of 7.5 mg daily.

• Route: Oral or intramuscular administration (oral being most common).

• Dosing Adjustments:

  • Use lower doses in patients with renal impairment; avoid in patients with severe renal or hepatic dysfunction.

• Maximum Safe Dose: 15 mg per day in adults.

7. Contraindications

• Absolute Contraindications:

  • Known hypersensitivity to meloxicam or other NSAIDs.

  • Active GI bleeding, peptic ulcer disease, or history of NSAID-induced GI bleeding.

  • Severe renal or hepatic impairment.

  • Cardiovascular disease in patients where NSAIDs are contraindicated.

• Relative Contraindications:

  • Asthma, especially in patients with aspirin-exacerbated respiratory disease.

  • Congestive heart failure and other significant cardiovascular conditions.

8. Warnings and Precautions

• Black Box Warnings:

  • Increased risk of serious cardiovascular events, including myocardial infarction and stroke, particularly with long-term use or in patients with cardiovascular disease.

  • Increased risk of gastrointestinal bleeding, ulceration, and perforation, which can be fatal.

• Special Warnings:

  • Use with caution in elderly patients and in those with a history of GI or cardiovascular disorders.

  • Avoid use in pregnancy, especially in the third trimester.

• Monitoring Parameters:

  • Monitor for signs of GI bleeding, liver function tests, renal function, and complete blood count during prolonged therapy.

9. Adverse Effects

• Common Adverse Effects (≥10%): GI discomfort (nausea, vomiting, abdominal pain), diarrhea, indigestion.

• Less Common but Clinically Significant: Edema, elevated liver enzymes, headache.

• Rare/Serious Adverse Reactions:

  • GI bleeding, ulcers, hepatotoxicity.

  • Severe skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis.

  • Cardiovascular events (e.g., myocardial infarction, stroke).

10. Drug Interactions

• Major Drug Interactions:

  • Anticoagulants (e.g., warfarin): Increased risk of bleeding.

  • ACE inhibitors/ARBs: May reduce the antihypertensive effect and increase risk of renal impairment.

  • Methotrexate: Risk of increased methotrexate toxicity.

• Food-Drug Interactions: Food does not significantly affect the absorption of meloxicam.

• Interactions with Lab Tests: May elevate liver enzymes and prolong bleeding time.

11. Clinical Pharmacology

• Meloxicam’s pharmacodynamics involve selective COX-2 inhibition, providing anti-inflammatory and analgesic effects with less gastrointestinal toxicity than non-selective NSAIDs. Its long half-life enables once-daily dosing, suitable for chronic conditions requiring regular dosing.

12. Special Populations

• Pregnancy: Not recommended, especially during the third trimester due to risks to the fetus (e.g., premature closure of the ductus arteriosus).

• Lactation: Limited data available; generally not recommended in breastfeeding mothers due to lack of safety data.

• Geriatrics: Increased risk of GI and renal side effects; use with caution and at the lowest effective dose.

• Renal/Hepatic Dysfunction: Avoid in severe renal or hepatic impairment. Dose adjustments are recommended in mild to moderate impairment.

13. Therapeutic Uses

• First-Line Therapy: Often used for chronic inflammatory conditions such as osteoarthritis and rheumatoid arthritis where longer-term NSAID therapy is appropriate.

• Second-Line or Adjunctive Therapy: May be used in combination with other analgesics in the management of pain, especially in inflammatory disorders.

14. Monitoring and Follow-Up

• Recommended Lab Tests: Periodic CBC, liver function tests, and renal function tests, especially in long-term therapy.

• Patient-Reported Symptom Checklists: Monitor for GI symptoms, signs of GI bleeding, or cardiovascular symptoms.

• Monitoring of Therapeutic and Toxic Levels: Regular clinical monitoring for signs of adverse effects, particularly in high-risk patients.

15. Overdose Management

• Symptoms of Overdose: Nausea, vomiting, abdominal pain, lethargy, dizziness; severe cases may lead to renal failure, respiratory depression, or coma.

• Treatment Protocols:

  • Activated charcoal if overdose is recent (within 1-2 hours).

  • Supportive care and symptomatic treatment (e.g., IV fluids).

  • Hemodialysis is generally ineffective due to high protein-binding.

16. Patient Counseling Information

• Advise patients to take meloxicam with food or milk to reduce gastrointestinal irritation.

• Inform patients of potential GI risks and to report symptoms such as black stools, severe abdominal pain, or chest pain immediately.

• Encourage patients to avoid other NSAIDs or aspirin unless specifically advised by their healthcare provider, as this may increase the risk of adverse effects.