Polmacoxib is a selective COX-2 inhibitor used for the treatment of osteoarthritis and rheumatoid arthritis. It belongs to the class of nonsteroidal anti-inflammatory drugs (NSAIDs) and provides pain relief with a lower risk of gastrointestinal side effects compared to traditional NSAIDs. It also shows carbonic anhydrase inhibitory activity, which may enhance its therapeutic effects. Polmacoxib was developed in South Korea and approved in 2015 by the country's Ministry of Food and Drug Safety (MFDS) for the treatment of osteoarthritis. It is marketed by CrystalGenomics under the brand name Acelex.
BRAND NAMES
Acelex: Acelex is the brand name for polmacoxib, a selective COX-2 inhibitor approved in South Korea in 2015 for the treatment of osteoarthritis. It is available as a 2 mg oral capsule, taken once daily.
MECHANISM OF ACTION
Polmacoxib selectively inhibits the COX-2 enzyme, which plays a key role in the conversion of arachidonic acid to prostaglandins that mediate inflammation, pain, and fever. By sparing COX-1, it helps minimize gastrointestinal side effects typically associated with non-selective NSAIDs. In addition, polmacoxib inhibits carbonic anhydrase isoenzymes I and II, which may promote accumulation in inflamed tissues such as joints, enhancing its local anti-inflammatory effect and possibly reducing systemic side effects. This dual mechanism contributes to its efficacy and improved safety profile.
PHARMACOKINETICS
Absorption
Polmacoxib is rapidly absorbed after oral administration, with peak plasma concentration (Tmax) reached in approximately 3 to 4 hours.
Distribution
Polmacoxib is highly bound to plasma proteins, mainly albumin, with a binding rate of over 95%. It has a moderate volume of distribution, indicating limited tissue penetration but effective delivery to target sites, especially inflamed joints due to carbonic anhydrase binding.
Metabolism
Polmacoxib is primarily metabolized in the liver, likely through cytochrome P450 (CYP) enzymes, and undergoes oxidation and conjugation to form inactive metabolites before being excreted.
Elimination
Polmacoxib has a half-life of approximately 10–12 hours, supporting once-daily dosing. It is eliminated mainly through the urine and feces in the form of metabolites.
DOSAGE AND ADMINISTRATION
The recommended dose of Polmacoxib is 2 mg once daily, taken orally with or without food. It should be swallowed whole with water and taken at the same time each day for consistent effect. Dose adjustments are not typically required in elderly patients but should be used with caution in those with hepatic or renal impairment. Treatment duration should be based on clinical need, using the lowest effective dose for the shortest duration to minimize risks.
DRUG INTERACTIONS
- Antihypertensives (e.g., ACE inhibitors, ARBs, diuretics): May reduce their effectiveness and increase the risk of kidney damage.
- Warfarin and other anticoagulants: May enhance bleeding risk; monitor INR closely.
- Other NSAIDs or aspirin: Increases risk of gastrointestinal side effects and bleeding.
- Cytochrome P450 substrates (e.g., CYP2C9, CYP3A4 drugs): Potential interaction due to hepatic metabolism; caution advised.
- Methotrexate: May increase methotrexate toxicity by reducing renal clearance.
- Lithium: Can increase lithium levels and toxicity risk.
- Diuretics: May reduce natriuretic effect and increase risk of renal impairment.
CONTRAINDICATIONS
- Hypersensitivity to polmacoxib or other sulfonamides.
- Active gastrointestinal bleeding or peptic ulcer.
- Severe hepatic or renal impairment.
- Congestive heart failure (NYHA class II–IV).
- Pregnancy and breastfeeding.
- Known cardiovascular disease or history of stroke.
SIDE EFFECTS
- Nausea, abdominal pain, and indigestion
- Headache, dizziness, and fatigue
- Skin rash, itching, or allergic reactions
- Edema, increased blood pressure, and risk of heart events
- Elevated liver enzymes and kidney function changes
- Diarrhea or constipation
- Respiratory symptoms in NSAID-sensitive individuals
TOXICITY
Polmacoxib toxicity may lead to gastrointestinal bleeding, cardiovascular events like heart attack or stroke, kidney damage, liver enzyme elevation, and central nervous system effects such as dizziness or confusion, especially at high doses or with prolonged use.
