Coxpar40 mg/vial

Coxpar is indicated for the following use:

Established / Approved Use

• Short-term management of postoperative pain in adults — Coxpar injection (intravenous or intramuscular) is approved for the short-term treatment of acute pain following surgery. It is intended for perioperative/inpatient use, typically for no more than a few days, and is often used as part of a multimodal analgesic regimen alongside opioids or other analgesics to reduce opioid requirements.

Not Established / Not Recommended

• Coxpar is not indicated for chronic pain conditions, long-term anti-inflammatory therapy, or outpatient/self-administered use. Its use is restricted to short-term, medically supervised, postoperative settings because of cardiovascular and gastrointestinal risks that increase with duration of use.

The decision to prescribe Coxpar should be based on an assessment of the individual patient's overall cardiovascular and gastrointestinal risk.

Each vial of Parecoxib injection contains Parecoxib sodium equivalent to 40 mg of Parecoxib as a sterile, white to off-white lyophilized (freeze-dried) powder for reconstitution into a solution for intravenous (IV) or intramuscular (IM) injection.

Parecoxib is the pro-drug of valdecoxib; after administration it is rapidly and almost completely hydrolyzed in the liver to valdecoxib, which is the pharmacologically active moiety responsible for its analgesic and anti-inflammatory effects.

Coxpar is a selective cyclo-oxygenase-2 (COX-2) inhibitor belonging to the "coxib" class of non-steroidal anti-inflammatory drugs (NSAIDs). Unlike oral coxibs, Coxpar is formulated exclusively as an injectable (IV/IM) product and is used in hospital/perioperative settings for the short-term treatment of acute postoperative pain.

Coxpar itself is inactive; it functions as a water-soluble pro-drug that is converted in the body to valdecoxib, a potent and selective COX-2 inhibitor. By selectively blocking COX-2 while largely sparing COX-1, Coxpar/valdecoxib reduces prostaglandin-mediated pain and inflammation while aiming to reduce (though not eliminate) the gastrointestinal ulcerogenic potential seen with non-selective NSAIDs.

Like other NSAIDs and COX-2 inhibitors, Coxpar carries a boxed-warning-level risk of serious cardiovascular thrombotic events and serious gastrointestinal bleeding, and its use is therefore restricted to short-term, medically supervised administration.

Coxpar belongs to the therapeutic class of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) — Selective Cyclo-oxygenase-2 (COX-2) Inhibitors (coxibs), injectable analgesic/anti-inflammatory agents.

Mechanism

Parecoxib is a pro-drug that is rapidly hydrolyzed in vivo (mainly hepatically) to valdecoxib, its active metabolite. Valdecoxib selectively inhibits cyclo-oxygenase-2 (COX-2), the enzyme responsible for converting arachidonic acid to prostaglandins at sites of inflammation and tissue injury, while having minimal effect on cyclo-oxygenase-1 (COX-1) at therapeutic doses. This selective inhibition reduces prostaglandin synthesis, producing analgesic, anti-inflammatory, and antipyretic effects without the marked platelet and gastric-mucosal COX-1 inhibition seen with non-selective NSAIDs.

Pharmacokinetics

• Onset: Analgesic effect begins within approximately 7–13 minutes of intravenous administration.
• Conversion: Parecoxib is converted to valdecoxib with a conversion half-life of about 22 minutes.
• Protein binding: Valdecoxib is highly (~98%) bound to plasma proteins.
• Metabolism: Valdecoxib is metabolized mainly via CYP3A4 and CYP2C9, with some non-CYP-mediated hydroxylation and glucuronidation.
• Elimination half-life: Approximately 8 hours for valdecoxib.
• Excretion: Primarily as inactive metabolites in urine.

Coxpar powder for injection must be reconstituted before use (see Reconstitution) and administered by a qualified healthcare professional.

• Intravenous (IV) injection: May be given as a rapid IV bolus injection directly into a vein or into an existing IV line.
• Intramuscular (IM) injection: Should be given slowly and deeply into a large muscle mass.
• Coxpar must not be administered by any route other than IV or IM (e.g., not for epidural, intrathecal, subcutaneous, or intra-arterial use).
• Coxpar should not be mixed with other medicinal products in the same syringe during reconstitution or injection unless compatibility has been established.
• Use the reconstituted solution promptly, in line with the reconstitution instructions and facility protocols.

Coxpar (via its active metabolite valdecoxib) has the following clinically significant interactions:

• Oral anticoagulants (e.g., warfarin): Concomitant use increases the risk of serious bleeding complications; INR and clinical status should be monitored closely, particularly when starting or stopping Coxpar.
• Other NSAIDs and aspirin (high-dose): Concurrent use should be avoided due to additive risk of gastrointestinal ulceration and bleeding without proven additional benefit. Low-dose cardioprotective aspirin may still be used, with awareness of increased GI risk.
• ACE inhibitors, angiotensin II receptor blockers, and diuretics: Coxpar may reduce their antihypertensive effect and, in patients with pre-existing renal impairment, volume depletion, or on diuretics, may increase the risk of acute renal function deterioration; renal function should be monitored.
• Lithium: Coxpar reduces renal clearance of lithium, increasing serum lithium levels and risk of toxicity; monitor lithium levels closely.
• Fluconazole (CYP2C9/3A4 inhibitor): Significantly increases plasma exposure to the active metabolite; a lower Coxpar dose should be considered when co-administered with fluconazole.
• CYP2D6 substrates with narrow therapeutic index (e.g., flecainide, certain antiarrhythmics/antidepressants): Valdecoxib can inhibit CYP2D6, potentially raising levels of these drugs; use with caution.
• Corticosteroids: Concurrent use increases the risk of gastrointestinal ulceration and bleeding.
• Cyclosporine and tacrolimus: Risk of additive nephrotoxicity; renal function should be monitored.

Serious / Boxed-Warning-Level Risks

• Cardiovascular thrombotic events: Increased risk of myocardial infarction and stroke, which can be fatal; risk increases with dose, duration of use, and pre-existing cardiovascular risk factors, and is markedly increased after CABG surgery.
• Serious gastrointestinal events: Bleeding, ulceration, and perforation of the stomach or intestines, which can occur without warning and can be fatal.
• Serious skin reactions: Rare but potentially life-threatening reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme have been reported.
• Anaphylaxis and severe hypersensitivity reactions.
• Renal effects: Fluid retention, edema, and acute deterioration of renal function, particularly in at-risk patients.

Common Side Effects

• Nausea and vomiting
• Insomnia
• Hypotension or hypertension
• Injection-site pain
• Pruritus (itching)
• Back pain
• Peripheral edema
• Dizziness and headache
• Elevated liver enzymes
• Hypokalemia

Pregnancy: Coxpar should be avoided during the first and second trimesters of pregnancy unless clearly necessary, and only if the potential benefit to the mother justifies the potential risk to the fetus; use in early pregnancy has been associated with increased risk of miscarriage. Like other NSAIDs, Coxpar is contraindicated during the third trimester because of the risk of premature closure of the fetal ductus arteriosus, oligohydramnios, and potential complications during labor and delivery. Coxpar should only be used in pregnancy under close medical supervision and after consulting a physician.

Lactation: Coxpar is contraindicated in breastfeeding women. Although the amount excreted into breast milk is small, safety in nursing infants has not been established, and a physician should be consulted before use in any breastfeeding mother; if treatment is essential, breastfeeding should be discontinued.

Cardiovascular Risk

Coxpar, like other NSAIDs and COX-2 inhibitors, may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use and in patients with existing cardiovascular risk factors or disease. Coxpar is contraindicated for the treatment of perioperative pain in the setting of CABG surgery. Cardiovascular risk should be assessed before prescribing Coxpar, and the lowest effective dose for the shortest duration should be used.

Gastrointestinal Risk

NSAIDs, including Coxpar, can cause serious GI adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal and can occur at any time, with or without warning symptoms. Elderly patients and those with a prior history of peptic ulcer disease or GI bleeding are at greater risk.

Renal Effects

Coxpar should be used with caution in patients with pre-existing renal impairment, heart failure, liver dysfunction, or volume depletion, and in those taking diuretics or ACE inhibitors/ARBs, as it may cause dose-dependent reduction in renal blood flow and precipitate acute renal failure. Renal function should be monitored in at-risk patients.

Fluid Retention and Hypertension

Fluid retention and edema have been observed; Coxpar should be used with caution in patients with fluid retention, hypertension, or heart failure.

Skin Reactions

Serious, potentially fatal skin reactions have been reported. Coxpar should be discontinued immediately at the first sign of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Duration and Setting of Use

Coxpar is intended only for short-term (typically inpatient/perioperative) use per its approved indication and is not intended for chronic administration. Concomitant use with other NSAIDs should be avoided.

There is limited clinical experience with Coxpar overdosage. Expected features would be an extension of known adverse effects, such as gastrointestinal bleeding, hypertension, acute renal impairment, and central nervous system effects.

There is no specific antidote for Coxpar overdose. In case of suspected overdose, seek immediate medical attention or contact a poison control center / emergency services. Management is supportive and symptomatic, based on the patient's clinical status; the active metabolite is highly protein-bound and is not expected to be significantly removed by hemodialysis.

Store Coxpar vials at room temperature (below 30°C), protected from light. Do not freeze. Once reconstituted, the solution should be used according to the healthcare facility's protocol and product-specific stability information, and should generally be used promptly rather than stored for extended periods. Keep out of reach of children.

Pediatric Patients

Safety and efficacy of Coxpar in patients under 18 years of age have not been established; its use in children and adolescents is not recommended.

Elderly Patients

Elderly patients are at greater risk for serious cardiovascular, gastrointestinal, and renal adverse reactions. No routine dose adjustment is required, but caution is advised, especially in patients weighing less than 50 kg, in whom a lower starting dose may be considered.

Renal Impairment

Use with caution and close monitoring in mild-to-moderate renal impairment; contraindicated in severe renal impairment or in patients at risk of significant volume depletion.

Hepatic Impairment

Dose reduction is recommended in moderate hepatic impairment; contraindicated in severe hepatic impairment.

Cardiovascular Disease

Contraindicated in patients with established ischemic heart disease, peripheral arterial disease, cerebrovascular disease, congestive heart failure (NYHA II-IV), and in the perioperative period of CABG surgery (see Contraindications).

Coxpar is intended strictly for short-term use in the management of acute postoperative pain. Clinical experience with treatment beyond 3 days is limited, and it should be given for the shortest duration consistent with the individual patient's treatment goals, using the lowest effective dose.

Coxpar 40 mg powder for injection must be reconstituted immediately before use, using an appropriate compatible diluent as specified in the product's reconstitution instructions (e.g., 0.9% sodium chloride injection, 5% dextrose injection, or sterile water for injection), to form a clear solution.

• Reconstitute only with a compatible diluent; do not mix with diluents or medicinal products not confirmed as compatible.
• Gently swirl until the powder is completely dissolved; do not shake vigorously.
• Inspect the reconstituted solution visually for particulate matter and discoloration before administration; discard if either is present.
• Use the reconstituted solution promptly; if not used immediately, storage time and conditions before use are the responsibility of the administering healthcare professional and should follow facility protocol.
• Reconstitution and administration should be performed by a trained healthcare professional under aseptic conditions.

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs); Selective COX-2 Inhibitors (Coxibs); Injectable Analgesic and Anti-inflammatory Agents

Parecoxib is a pro-drug that is rapidly hydrolyzed in the liver to valdecoxib, its pharmacologically active form. Valdecoxib selectively and reversibly inhibits the cyclo-oxygenase-2 (COX-2) enzyme, reducing the synthesis of prostaglandins that mediate pain, inflammation, and fever at the site of tissue injury, while sparing cyclo-oxygenase-1 (COX-1) at therapeutic concentrations, which is responsible for protective gastric mucosal and platelet function.

The safety and efficacy of Coxpar have not been established in pediatric patients (under 18 years of age). Coxpar is therefore not recommended for use in children or adolescents, and should only be used in adults for the approved short-term postoperative pain indication.