Parecoxib

Indications

Parecoxib is used for: Short-term treatment of acute pain & post-op pain ie, oral surgery, abdominal hysterectomy, myomectomy, total knee replacement, total hip arthroplasty, laparoscopic cholecystectomy, inguinal hernia repair & other general surgery eg, diagnostic laparoscopy, gastrectomy, hernioplasty, appendectomy, hemithyroidectomy & splenectomy. Pre-op to prevent or reduce post-op pain & reduce opioid requirements when used concomitantly.

Adult Dose

Parenteral IV/IM Adult: Management of acute pain Initially 40 mg followed by 20 or 40 mg every 6-12 hr as required. Max: 80 mg/day. Prevention or reduction of post-op pain 40 mg 30-45 min prior to surgical incision, may be continued post-op as needed for adequate effect. Elderly <50 kg Reduce initial dose by 50%. Max: 40 mg/day. Predisposed to fluid retention, co-administration w/ fluconazole Lowest recommended dose. Hepatic Impairment Mild (Child-Pugh score 5-6): No dosage adjustment needed. Moderate (Child-Pugh score 7-9): Half the usual dose. Max: 40 mg/day. Severe (Child-Pugh score >10): Contraindicated.

Child Dose

Renal Dose

Severe renal impairment (CrCl <30 mL/min) Lowest recommended dose.

Administration

Reconstitute w/ either NaCl 0.9%, glucose 5%, or NaCl 0.45% w/ glucose 5%.

Contra Indications

Hypersensitivity to parecoxib or sulfonamides. History of previous serious allergic reaction of any type, especially cutaneous reactions eg, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme. Patients w/ history of CVA, MI, CABG, uncontrolled HTN, CHF (NYHA II-IV). Active peptic ulceration or GI bleeding. Patients who have experienced bronchospasm, acute rhinitis, nasal polyps, bronchial asthma, angioneurotic edema, urticaria or other allergic-type reactions after taking aspirin or NSAIDs including other COX-2 inhibitors. Severe hepatic dysfunction (serum albumin <25 g/L or Child-Pugh Class C). Inflammatory bowel disease. Treatment of post-op pain immediately following CABG surgery. Established ischemic heart disease, peripheral arterial disease &/or cerebrovascular disease. Pregnancy (3rd trimester) & lactation.

Precautions

Administration other than IV or IM. Increased risk of CV & thrombotic adverse events associated w/ COX-2 inhibitors when taken long term appears to be similar in those w/ or w/o known CV disease or CV risk factors. Most at risk of developing GI complications w/ NSAIDS are the elderly, patients w/ CV disease, concomitant use w/ aspirin, corticosteroids, SSRIs or other NSAIDs, or alcohol intake or w/ history or active GI disease eg, ulceration, bleeding or inflammatory conditions. W/ or w/o history of sulfonamide allergy. Discontinue use at the 1st appearance of skin rash, mucosal lesions or any other sign of hypersensitivity. Severe hypotension may occur. Concomitant use w/ anticoagulants. Can lead to the onset of new HTN or worsening of preexisting HTN. Monitor BP closely during initiation of & throughout the course of therapy. Compromised cardiac function, preexisting edema, or other conditions predisposing to, or worsened by, fluid retention including those on diuretic therapy or at risk of hypovolemia. Monitor renal function closely in patients w/ advanced renal disease. Rehydrate patients prior to & at initiation of therapy. Moderate hepatic impairment (Child-Pugh Class B). May diminish the utility of diagnostic signs eg, fever in detecting infections; avoid concomitant use w/ other non-specific NSAIDs. Consider withdrawal in women who have difficulties conceiving or who are undergoing infertility investigation. Pregnant women on parecoxib should be closely monitored for amniotic fluid vol. Lactation. Childn <18 yr.

Pregnancy-Lactation

Fertility: Based on the mechanism of action, the use of NSAIDs may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of NSAIDs, including parecoxib, should be considered. Pregnancy: There were no findings of teratogenicity in studies in rats and rabbits. Studies in rats at maternally toxic doses and studies in rabbits at the maximal evaluable dose have not revealed embryotoxic effects other than post-implantation loss, which has been observed with other drugs that inhibit prostaglandin synthesis. There are no studies in pregnant women. Parecoxib should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. As with other drugs known to inhibit prostaglandin synthesis, use of parecoxib during the third trimester of pregnancy should be avoided because it may cause uterine inertia and premature closure of the ductus arteriosus. Inhibition of prostaglandin synthesis might adversely affect pregnancy. Data from epidemiological studies suggest an increased risk of spontaneous abortion after use of prostaglandin synthesis inhibitors in early pregnancy. In animals, administration of prostaglandin synthesis inhibitors has been shown to result in increased pre- and post-implantation loss. If used during second or third trimester of pregnancy, NSAIDs may cause fetal renal dysfunction which may result in reduction of amniotic fluid volume or oligohydramnios in severe cases. Such effects may occur shortly after treatment initiation and are usually reversible. Pregnant women on parecoxib should be closely monitored for amniotic fluid volume. Lactation: Parecoxib and its active metabolite are excreted in the milk of lactating rats. Administration of a single dose of parecoxib to lactating women resulted in the transfer of a relatively small amount of parecoxib and its active metabolite into breast milk, and this resulted in a low relative dose for the infant (less than 1% of the weight-adjusted maternal dose). Because of the potential for adverse reactions in nursing infants from parecoxib, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Interactions

Increased AUC w/ CYP3A4 & 2C9 inhibitors. Increased risk of bleeding w/ oral anticoagulants including warfarin/coumarin-type & novel oral anticoagulants (eg, apixaban, dabigatran & rivaroxaban). Enhanced AUC w/ fluconazole & ketoconazole. May diminish effects of ACE inhibitors, angiotensin II antagonists, beta-blockers & diuretics. May reduce natriuretic effect of furosemide & thiazides. Increased risk of nephrotoxicity w/ cyclosporine. May increase plasma levels of methotrexate. Decreased lithium serum & renal clearance.

Side Effects

Side effects of Parecoxib : Nausea, pharyngitis, alveolar osteitis (dry socket), anaemia post-op, hypokalaemia, agitation, insomnia, hypoaesthesia, dizziness, HTN, hypotension, resp insufficiency, abdominal pain, vomiting, constipation, dyspepsia, flatulence, pruritus, hyperhidrosis, back pain, oliguria, peripheral oedema, MI, deep-vein thrombosis, pulmonary embolism, stroke, deep surgical infections, sternal wound complications, renal impairment, increased blood creatinine. Potentially Fatal: Anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Mode of Action

Parecoxib is the prodrug of valdecoxib. It is a selective cyclo-oxygenase-2 (COX-2) inhibitor primarily responsible to reduce mediators of pain and inflammation. Its action is due to inhibition of prostaglandin synthesis via inhibition of COX-2.