Olicoxib Special Precautions

The decision to prescribe a selective COX-2 inhibitor should be based on an assessment of the individual patient's overall risks (see Contraindications).
Administration Other Than IV or IM: Modes of administration other than IV or IM (e.g. intra-articular, intrathecal) have not been studied and should not be used.
Cardiovascular Adverse Effects: All NSAIDs, including COX-2 inhibitors, of which parecoxib is one, have been associated with an increased risk of cardiovascular and thrombotic adverse events when taken long term. The relative increase of this risk appears to be similar in those with or without known CV disease or CV risk factors. However, patients with known cardiovascular disease or CV risk factors may be at greater risk in terms of absolute incidence, due to their increased rate at baseline.
Patients treated with Parecoxib sodium for pain immediately following CABG surgery have a higher risk for CV/thromboembolic events, deep surgical infections or sternal wound healing complications. This was seen more often in elderly patients (>65 years old) or patients with a history of peripheral vascular or cerebrovascular disease or poor post-surgical renal function (see Pharmacology: Pharmacodynamics: Special Studies: CABG Post-operative Safety Studies under Actions).
OLICOXIB is therefore contraindicated for the treatment of post-operative pain following CABG surgery (see Contraindications).
Parecoxib sodium has not been studied in other cardiovascular surgical procedures.
In an analysis of non-cardiac surgery controlled trials, patients treated with parecoxib did not experience an increased risk of CV adverse events compared with placebo.
However, patients with significant and multiple risk factors for CV events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking) should only be treated with parecoxib sodium after careful consideration (see Pharmacology: Pharmacodynamics: Special Studies: General Surgery under Actions).
All patients should receive the lowest dose effective in relieving symptoms. The dose should not exceed 40 mg.
Serious Skin Reactions: Serious skin reactions including erythema multiforme and Stevens-Johnson syndrome have been reported through post-marketing surveillance in patients receiving parecoxib. In addition to erythema multiforme and Stevens-Johnson syndrome, exfoliative dermatitis and toxic epidermal necrolysis have been reported through post-marketing surveillance in patients receiving valdecoxib. Fatalities due to Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported with valdecoxib and the potential cannot be ruled out for parecoxib (the prodrug of valdecoxib). Generalised bullous fixed drug eruption (GBFDE) may occur with parecoxib exposure based on a reaction with etoricoxib exposure. Drug reaction with eosinophilia and systemic symptoms syndrome (DRESS syndrome) may occur with parecoxib exposure based on other serious skin reactions reported with celecoxib and valdecoxib exposure (see Post-Marketing Experience under Adverse Reactions). Patients appear to be at highest risk for these events early in the course of therapy; with the onset of the event occurring in the majority of cases in the first two weeks of treatment. OLICOXIB Injection should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity. Serious skin reactions have been reported with other COX-2 inhibitors during post-marketing experience.
Valdecoxib, the active moiety of parecoxib, contains a sulfonamide moiety. Patients with a history of sulfonamide allergy may be at a greater risk for skin reactions, however, patients without a history of sulfonamide allergy may also be at risk.
Anaphylactoid Reactions: Anaphylactoid reactions were not reported in patients receiving Parecoxib sodium Injection in clinical trials. However, as with NSAIDs in general, anaphylactoid reactions may occur in patients without known prior exposure to Parecoxib sodium Injection. OLICOXIB Injection should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs (see Contraindications and Pre-existing Asthma as follows). Emergency help should be sought in cases where an anaphylactoid reaction occurs.
Hypersensitivity reactions (anaphylactic reactions and angioedema) have been reported in post-marketing experience with valdecoxib and parecoxib (see Post-Marketing Experience under Adverse Reactions). These reactions have occurred in patients with and without a history of allergic-type reactions to sulfonamides (see Contraindications). Parecoxib should be discontinued at the first sign of hypersensitivity.
General: OLICOXIB Injection may mask fever. The concomitant use of parecoxib with other non-specific NSAIDs should be avoided.
In addition, caution should be exercised with respect to monitoring the incision for signs of infection in patients receiving OLICOXIB Injection. When used in post-CABG patients at a dose of 80 mg/day over 14 days, no increase in overall infection rate was seen. However, sternal wound infections occurred at a somewhat higher rate in patients receiving Parecoxib sodium compared to placebo (Parecoxib sodium 2.6%, placebo 2.0%, p=NS).
In the repeated dose toxicity studies in dogs and rats, the systemic exposures to valdecoxib (the active metabolite of parecoxib) were approximately 0.8-fold the systemic exposure in elderly human subjects at the maximum recommended therapeutic dose of 80 mg daily. Higher doses were associated with aggravation and delayed healing of skin infections, an effect probably associated with COX-2 inhibition.
Gastrointestinal Effects - Risk of GI Ulceration, Bleeding, and Perforation: It is unclear, at the present time, how the rates of serious GI toxicity associated with NSAIDs that inhibit both COX-1 and COX-2, apply to OLICOXIB Injection. Parecoxib sodium Injection, a COX-2 specific inhibitor, does not affect COX-1 function as demonstrated by relevant clinical results.
Serious Gl toxicity such as bleeding, ulceration, and perforation of the stomach, small intestine or large intestine, can occur at any time, with or without warning symptoms, in patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs), including OLICOXIB Injection. Minor upper Gl problems, such as dyspepsia, are common and may also occur at any time during NSAID therapy. Therefore, physicians and patients should remain alert for ulceration and bleeding, even in the absence of previous GI tract symptoms. Patients should be informed about the signs and/or symptoms of serious Gl toxicity and the steps to take if they occur. The utility of periodic laboratory monitoring has not been demonstrated, nor has it been adequately assessed. Only one in five patients who develop a serious upper Gl adverse event on NSAID therapy is symptomatic. It has been demonstrated that upper Gl ulcers, gross bleeding or perforation, caused by NSAIDs, appear to occur in approximately 1% of patients treated for 3-6 months, and in about 2-4% of patients treated for one year. These trends continue thus, increasing the likelihood of developing a serious Gl event at some time during the course of therapy. However, even short-term therapy is not without risk.
The ulcerogenic effects of Parecoxib sodium Injection and oral valdecoxib on the upper GI tract were examined in short-term (7 day) studies in young and elderly healthy subjects, and a 12-week study in OA patients, respectively. Significantly fewer endoscopically detected ulcers were seen with Parecoxib sodium Injection compared to ketorolac and naproxen, and with valdecoxib compared to ibuprofen and naproxen (see Pharmacology: Pharmacodynamics: Clinical Trials and Special Studies under Actions).
Patients most at risk of developing Gl complications with NSAIDs are elderly patients; patients with cardiovascular disease; patients using concomitant aspirin, corticosteroids, selective serotonin reuptake inhibitors (SSRIs) or other NSAIDs; patients ingesting alcohol; and patients with a history of, or active, GI disease (such as ulceration, bleeding or inflammatory conditions). In addition, pharmaco-epidemiological studies have identified several other co-therapies or co-morbid conditions that may increase the risk for GI bleeding such as: treatment with anticoagulants, longer duration of NSAID therapy, smoking, alcoholism, and poor general health status. OLICOXIB Injection should be prescribed with caution in these patients. Physicians and patients should remain alert for ulceration and bleeding even in the absence of symptoms.
Most spontaneous reports of fatal Gl events are in elderly or debilitated patients and therefore special care should be taken in treating this population. To minimise the potential risk for an adverse GI event, the lowest effective dose should be used for the shortest possible duration. For high-risk patients, alternate therapies that do not involve NSAIDs should be considered. Studies have shown that patients with a prior history of peptic ulcer disease and/or GI bleeding and who use NSAIDs, have a greater than 10-fold higher risk for developing a GI bleed than patients with neither of these risk factors.
Use in hepatic impairment: Borderline elevations of one or more liver function tests were observed in 3.4% of surgical patients receiving Parecoxib sodium Injection and 5.8% of placebo patients. Notable elevations (greater than three or more times the Upper Limit of Normal) were seen in 0.7% of patients treated with Parecoxib sodium Injection and 0.8% of placebo patients.
Rare cases of severe hepatic reactions, including jaundice, fatal fulminant hepatitis, liver necrosis, hepatic failure (some with fatal outcome), and liver transplant have been reported with NSAIDs. In post-marketing experience, rare cases of jaundice, hepatomegaly, and hepatic failure have been reported with Parecoxib sodium Injection (see Post-Marketing Experience under Adverse Reactions).
A patient with symptoms and/or signs suggesting hepatic dysfunction, or in whom an abnormal liver function test has occurred, should be evaluated for evidence of the development of a hepatic reaction while on therapy with OLICOXIB Injection. If clinical signs and symptoms consistent with hepatic disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), OLICOXIB Injection should be discontinued.
Use in renal impairment: Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a non-steroidal anti-inflammatory drug may cause a dose-dependent reduction in renal prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics, ACE inhibitors, or angiotensin receptor antagonists, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pre-treatment state. Clinical trials with valdecoxib have shown renal effects similar to those observed with comparator NSAIDs.
Caution should be used when initiating treatment with OLICOXIB Injection in patients with considerable dehydration. It is advisable to rehydrate patients first and then start therapy with OLICOXIB Injection.
Caution is also recommended in patients with pre-existing renal disease. Even though, pharmacokinetically, there was no difference in excretion, in patients with severe renal disease treatment with OLICOXIB Injection should be initiated with caution. Close monitoring of the patient's renal function is advisable.
Acute renal failure has been reported through post-marketing surveillance in patients receiving parecoxib (see Adverse Reactions).
Concomitant Use of ACE inhibitors or Angiotensin Receptor Antagonists and Anti-inflammatory Drugs and Thiazide Diuretics: The use of an ACE inhibiting medicine (ACE-inhibitor or angiotensin receptor antagonist), and an anti-inflammatory drug (NSAID or COX-2 inhibitor) and a thiazide diuretic at the same time, increases the risk of renal impairment. This includes use in fixed-combination products containing more than one class of medicine. Concomitant use of all three classes of these medications should be accompanied by increased monitoring of serum creatinine, particularly at the institution of the treatment. The concomitant use of medicines from these three classes should be used with caution particularly in elderly patients or those with pre-existing renal impairment (see Anti-hypertensives including ACE-inhibitors, Angiotensin Receptor Antagonists, Beta Blockers and Diuretics under Interactions).
Concomitant Use of Oral Anticoagulants: The concomitant use of NSAIDs with oral anticoagulants increases the risk of bleeding (see Anticoagulants under Interactions). Oral anticoagulants include warfarin/coumarin-type and novel oral anticoagulants (e.g. apixaban, dabigatran, and rivaroxaban).
Hypertension: As with all NSAIDs, parecoxib can lead to the onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of cardiovascular events. NSAIDs, including parecoxib, should be used with caution in patients with hypertension. Blood pressure should be monitored closely during the initiation of therapy with parecoxib and throughout the course of therapy.
Severe Hypotension: Cases of severe hypotension shortly following parecoxib administration have been reported in postmarketing experience with parecoxib. Some of these cases have occurred without other signs of anaphylaxis. The practitioner should be prepared to treat severe hypotension.
Fluid Retention and Oedema: Fluid retention and oedema have been observed in <1.0% of patients undergoing general surgery who received Parecoxib sodium Injection, similar to placebo. OLICOXIB Injection should be used with caution in patients with compromised cardiac function, pre-existing oedema, or other conditions predisposing to, or worsened by, fluid retention including those taking diuretic treatment or otherwise at risk of hypovolaemia.
Pre-existing Asthma: Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm, which can be fatal. Since cross reactivity, including bronchospasm, between aspirin and other non-steroidal anti-inflammatory drugs has been reported in such aspirin-sensitive patients, OLICOXIB should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with pre-existing asthma (see Contraindications and Anaphylactoid Reactions as previously mentioned).
Effects on laboratory tests: Isolated laboratory abnormalities following surgery were seen in patients taking Parecoxib sodium Injection, placebo and comparators. No particular testing, other than appropriate post-operative laboratory monitoring, is indicated in patients receiving OLICOXIB Injection.
Effects on Ability to Drive and Use Machines: The effect of Parecoxib sodium Injection on ability to drive or use machinery has not been studied. However, patients who experience dizziness, vertigo or somnolence after receiving OLICOXIB Injection should refrain from driving or operating machinery.
Use in Children: Safety and effectiveness in paediatric patients below the age of 18 have not been evaluated.
Use in the Elderly: Of the total number of patients who received Parecoxib sodium Injection in clinical trials, more than 250 were 65-74 years of age, while approximately 70 additional patients were 75 years and over. No overall differences in safety and effectiveness between these patients and younger patients have been identified, but greater sensitivity of some older individuals cannot be ruled out.