Indications
Meloxicam is primarily indicated for the symptomatic treatment of arthritis and osteoarthritis. It is also approved for use in managing pauciarticular and polyarticular courses of Juvenile Rheumatoid Arthritis (JRA) in patients aged two years and older. Additionally, meloxicam has been utilized off-label for treating dental or post-surgical pain and has undergone studies for its efficacy in alleviating neuropathic pain. In combination with bupivacaine, meloxicam provides postsurgical analgesia in adult patients for up to 72 hours following various soft tissue and orthopedic surgical procedures, especially where direct exposure to articular cartilage is avoided.
Pharmacodynamics
Meloxicam is an anti-inflammatory and analgesic agent with antipyretic properties. It operates by exerting selective actions against the cyclooxygenase-2 (COX-2) enzyme, thereby mitigating inflammation and potentially reducing gastrointestinal side effects associated with non-selective NSAIDs. Clinical studies have shown that meloxicam effectively decreases erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels in patients with rheumatoid arthritis. However, like other NSAIDs, extended usage of meloxicam may lead to renal insufficiency, cardiovascular complications, or thrombotic events. While it tends to cause fewer gastrointestinal issues compared to other NSAIDs, meloxicam still poses a risk for gastric irritation, bleeding, and ulceration.
Absorption
Meloxicam exhibits high oral bioavailability, with an absorption rate of 89% following administration of oral capsules. The maximum concentration (Cmax) is typically reached 5 to 6 hours post-administration after a meal, and this Cmax may double when taken on an empty stomach. Meloxicam can be administered regardless of food intake, setting it apart from many other NSAIDs that require food to mitigate gastrointestinal discomfort. When formulated with bupivacaine, meloxicam shows varying systemic absorption profiles depending on the surgical procedure, with noted differences in parameters such as Cmax and time to reach it (Tmax) across different dosages.
Metabolism
Meloxicam undergoes extensive metabolism, predominantly via the cytochrome P450 enzyme CYP2C9, with minor involvement from CYP3A4. It produces four main metabolites, none of which possess biological activity. Approximately 60% of meloxicam is converted into 5'-carboxy meloxicam after undergoing hepatic cytochrome-mediated oxidation of its intermediate state, 5'-hydroxymethylmeloxicam. Two additional metabolites are likely formed through peroxidation processes. This thorough metabolism leads to effective drug clearance and impacts its pharmacokinetic profile.
Mechanism of Action
Meloxicam functions by inhibiting the enzymes cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), resulting in a reduced synthesis of prostaglandins, which are typically responsible for mediating painful inflammatory symptoms. By diminishing prostaglandin production, meloxicam effectively decreases the sensitization of neuronal pain receptors, thereby providing analgesic and anti-inflammatory effects. Although meloxicam exhibits a preferential inhibition of COX-2, it also impacts COX-1, which can lead to gastrointestinal irritation.
