What Is Etoricoxib?

Retorcoxib is used to treat the symptoms and signs of acute and chronic osteoarthritis, and to treat acute gouty arthritis. The prescription of cyclooxygenase-2 inhibitors should be given a comprehensive assessment of the risk of individual patients.

Drug Name: Cortox
Foreign name: etoricoxib

Dosage form: tablet
Whether to include health insurance: Not included
Drug type: Choose cyclooxygenase-2 inhibitors

Relying on Cortex Basic Information

Chinese name:

Chinese alias: 2,3'-bipyridine, 5-chloro-6'-methyl-3- [4- (methylsulfonyl) phenyl]; etocoxib; 5-chloro-2- (6-methyl Pyridyl-3-yl) -3- (4-methylsulfonylphenyl) pyridine

English name: etoricoxib

English alias: Etoricoxibe; Tauxib; Etoricoxib; Algix; 5-chloro-2- (6-methylpyridin-3-yl) -3- (4-) pyridine

CAS number: 202409-33-4

Molecular formula: C ₁₈ H ₁₅ ClN ₂ O ₂ S

Molecular weight: 358.84200

Exact mass: 358.05400

PSA: 68.30000

LogP: 5.25670

Structural formula:

Physical and chemical properties

Appearance and properties: off-white powder

Density: 1.298 g / cm ³

Melting point: 134-135 ° C

Boiling point: 510ºC at 760 mmHg

Flash point: 262.2ºC

Refractive index: 1.6

Vapor pressure: 5.17E-10mmHg at 25 ° C

Relying on Cortix Safety Information

Customs Code: 2933399090

WGK Germany: 3

Danger category code: R36 / 37/38

Safety instructions: S26; S36

Dangerous goods mark: Xi ^[1]

Relying on Cortex molecular structure data

1. Molar refractive index: 94.65

2. Molar volume (cm ³ / mol): 276.4

3. Isometric Zhang Rong (90.2K): 733.9

4. Surface tension (dyne / cm): 49.6

5. Polarizability (10-24cm ³ ): 37.52

Relying on Corxima to calculate chemical data

1. Hydrophobic parameter calculation reference value (XlogP): 3.3

2. Number of hydrogen-bonded donors: 0

3. Number of hydrogen bond acceptors: 4

4. Number of rotatable chemical bonds: 3

5. Number of tautomers: none

6. Topological molecular polar surface area 68.3

7. Number of heavy atoms: 24

8. Surface charge: 0

9. Complexity: 514

10. Number of isotope atoms: 0

11. Determine the number of atomic stereocenters: 0

12. Uncertain number of atomic stereocenters: 0

13. Determine the number of chemical bond stereocenters: 0

14. Uncertain number of chemical bond stereocenters: 0

15. Number of covalent bond units: 1 ^[2]

Relying on coxoxid production methods

Magnesium and 4-methylthiobenzyl chloride were dissolved in tetrahydrofuran to carry out the reaction. The reaction solution was added to Weinrebamidide and toluene to react. Aqueous acetic acid was added, followed by water and toluene. The layers were separated and the aqueous layer was extracted with toluene. The toluene layers were combined and extracted with dilute hydrochloric acid. Ethyl acetate was added to the extract, and the pH of the aqueous layer was adjusted with ammonia. The layers were separated and the aqueous layer was extracted with ethyl acetate. The ethyl acetate layers were combined and concentrated to give a pale yellow solid. This solid and sulfuric acid were dissolved in methanol, heated, and an aqueous solution of sodium tungstate was added, followed by reaction with hydrogen peroxide. Add water and cool to room temperature and filter. The solid was washed with water and dried under vacuum to obtain a ketosulfone compound. The ketosulfone compound, n-propionic acid and 3-amino-2-chloroacrylaldehyde, methanesulfonic acid and propionic acid are dissolved in toluene, refluxed, and azeotropically dehydrated. After cooling, isopropyl acetate was added, water was added, and the aqueous layer was neutralized with concentrated ammonia water. The separated organic layer was washed with a brine-water mixture and washed with water. The aqueous layers were combined and washed with isopropyl acetate. The organic layers were combined, treated with DarcoG 60, concentrated, and then recrystallized from isopropyl acetate-hexane to give etaxib.

Relying on Cortisol use

It is a second-generation cyclooxygenase-2 (COX-2) inhibitor. For the relief of osteoarthritis and rheumatoid arthritis symptoms, acute pain associated with dental surgery and primary dysmenorrhea.

Cortisol Cortisol Related drug label information

Cortisol drug name

Cortisol tablets

Cortisol ingredients

The main ingredient is relying on Cortisol,

Chemical name: 5chloro6methyl3 [4 (methanesulfonyl) phenyl] 2,3'bipyridine

Chemical Structure:

Molecular formula: C ₁₈ H ₁₅ ClN ₂ O ₂ S

Molecular weight: 358.84

Cortisol Traits

30mg: blue-green, apple-shaped double-convex film-coated tablet with ARCOXIA 30 engraved on one side and 101 on the other side;

60mg: dark green, apple-shaped biconvex film-coated tablet with ARCOXIA 60 engraved on one side and 200 on the other;

90mg: white, apple-shaped double-convex film-coated tablet with ARCOXIA 90 engraved on one side and 202 on the other;

120mg: light green, apple-shaped lenticular film-coated tablet with ARCOXIA 120 engraved on one side and 204 on the other.

Relicox indication

This product is suitable for treating the symptoms and signs of acute and chronic osteoarthritis; treating acute gouty arthritis

Relying on Cortisol specifications

(1) 30mg (2) 60mg (3) 90mg (4) 120mg

Reliance on Cortisol dosage

This product is for oral administration and can be taken with or without food.

arthritis

Osteoarthritis < br The recommended dose is 30mg once daily. For patients whose symptoms are not fully relieved, it can be increased to 60 mg once daily. When using this product 60mg once a day, after 4 weeks the effect is still not obvious, other treatments should be considered.

Acute gouty arthritis < br The recommended dose is 120 mg once daily. 120mg of this product is only suitable for acute onset of symptoms, the longest use is 8 days. When the dose is greater than the recommended dose, better efficacy has not been demonstrated or studies have not been conducted. Therefore, the maximum recommended dose for the treatment of osteoarthritis is no more than 60 mg per day. The maximum recommended dose for the treatment of acute gouty arthritis is no more than 120 mg per day. Because the cardiovascular risk of selective cyclooxygenase-2 inhibitors increases with higher doses and longer duration of medication, the duration of medication should be minimized and the lowest effective daily dose should be used. The patient's symptoms and response to treatment should be evaluated regularly.

Elderly, gender, ethnicity < br The elderly, people of different genders and ethnicities do not need to adjust the dose.

Liver insufficiency < br For patients with mild liver insufficiency (Child-Pugh score 5-6), the dosage of this product should not exceed 60mg once a day. Patients with moderate hepatic insufficiency (Child-Pugh score 7-9) should be reduced, should not exceed the dose of 60mg every other day, and the daily dosage of 30mg can be considered. For patients with severe liver dysfunction (Child-Pugh score> 9), no clinical or pharmacokinetic data are available.

Renal insufficiency

This product is not recommended for patients with advanced kidney disease (creatinine clearance <30mL / min). No dose adjustment is necessary for patients with mild renal insufficiency (creatinine clearance 30mL / min).

Reliance on Cortisol:

The following patients are prohibited from using this product: they are allergic to any one of its ingredients. Patients with active gastrointestinal ulcer / bleeding, or previous recurrent ulcer / bleeding. Patients who have asthma, urticaria, or allergic reactions after taking aspirin or other non-steroidal anti-inflammatory drugs. Congestive heart failure (New York Heart Association [NYHA] Heart Function Classification II-IV). Diagnosed ischemic heart disease, peripheral arterial disease, and / or cerebrovascular disease (including patients who have recently undergone coronary artery bypass grafting or angioplasty).

Medications for pregnant and lactating women relying on cortisol:

Pregnant woman

This product, like other drugs known to inhibit prostaglandin synthesis, can cause arterial catheters to close prematurely. Avoid using this product in late pregnancy.

Reproductive studies in rats have shown that when using this product at a dose of up to 15 mg / kg / day [equivalent to 1.5 times the human dose (90mg)], no developmental abnormalities were found. In the experimental study of rabbits treated with etoricoxib, the incidence of cardiovascular malformations and post-implantation abortions was increased at a dose equivalent to twice the human dose (90 mg), but the incidence was low. No developmental abnormalities were found at doses approximately equal to or lower than the daily human dose (90 mg). But animal reproduction research does not always predict human responses. There are currently no adequate, strictly controlled studies in pregnant women. Therefore, in the first 6 months of pregnancy, this product should only be used when the possible benefits outweigh the potential danger to the fetus.

Lactating women

This product can be secreted with the milk of lactating rats. It is unclear whether this product is secreted by human milk. Because many drugs can be secreted from human milk, and drugs that inhibit the synthesis of prostaglandin may have adverse effects on lactating infants, the importance of the drug to the mother should be carefully considered to decide whether to stop breastfeeding or discontinue this product.

Medication for children

This product has not yet established safety and efficacy in pediatric patients.

Geriatric medication

The pharmacokinetics of the elderly (65 years and older) are similar to those of the young. Clinical studies have shown that older patients have a higher incidence of adverse events than younger patients; the difference between the etoxic and control groups is similar for older and younger patients. It cannot be ruled out that some elderly patients have higher sensitivity.

Etoricoxib drug interactions

Warfarin -Long-term use of warfarin to treat stable patients, the international standardized ratio (INR) of prothrombin time 120mg per day increased by about 13%. In patients receiving warfarin or similar drugs, the INR value should be monitored when starting treatment with this product or changing the treatment regimen, especially during the first few days.
Rifampicin -Rifampicin is a strong inducer of liver metabolism. Combining this product with this product can reduce the area under the plasma curve (AUC) of this product by 65%. When this product is combined with rifampicin, its interaction should be considered.
Methotrexate -Two studies have observed the use of methotrexate 7.5 mg to 20 mg once a week in patients with rheumatoid arthritis who received 60, 90 or 120 mg of this product once a day for 7 consecutive days. This product has no effect on methotrexate plasma concentration (determining AUC) and renal clearance at 60 and 90 mg levels. In one of the studies, 120 mg of this product had no effect on the methotrexate plasma concentration (measurement of AUC) or renal clearance. In another study, 120mg of this product increased the plasma concentration of methotrexate by 28% (measured by AUC) and reduced the renal clearance of methotrexate by 13%. When the dosage of this product is greater than 90mg / day and combined with methotrexate, monitoring of methotrexate-related toxicity should be considered.
Diuretics, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin II antagonists (AIIAs)-There are reports that non-steroidal anti-inflammatory drugs, including selective inhibitors of cyclooxygenase-2, can reduce diuretics, Antihypertensive effect of angiotensin-converting enzyme inhibitors and angiotensin II antagonists. When this product is used simultaneously with these products, their interaction should be considered.

Some patients with renal insufficiency being treated with non-steroidal anti-inflammatory drugs including selective cyclooxygenase-2 inhibitors (for example, elderly patients or patients with hypoemia, including those receiving diuretics), The combination of angiotensin-converting enzyme inhibitors or angiotensin II antagonists may cause further impairment of renal function, including possible acute renal failure. But these effects are usually reversible. Therefore, concomitant medication should be used with caution, especially in elderly patients.
Lithium salts -There are reports that non-selective non-steroidal anti-inflammatory drugs and cyclooxygenase-2 selective inhibitors can increase lithium salt plasma levels. For patients taking both this product and lithium salts, this interaction should be considered.
Aspirin -This product can be used simultaneously with low-dose aspirin to prevent cardiovascular events. However, when combined with low-dose aspirin, the incidence of gastrointestinal ulcers or other complications is increased compared to the use of this product alone. In a stable state, this product 120mg once daily has no effect on the antiplatelet activity of a small dose of aspirin (81mg once daily) (cautions).
Oral contraceptives -simultaneous application of 60 mg of this product and 35 micrograms of ethinyl estradiol (EE) and 0.5 to 1 mg of norethisterone oral contraceptives for 21 consecutive days can increase the AUC at steady state EE by _0-24hr by 37% ; Taking 120mg of this product and the same oral contraceptive at the same time or at intervals of 12 hours, can increase the AUC 0-50% under steady state of EE by 50-60%; when choosing the appropriate oral contraceptive and taking this product at the same time, you need to consider To EE concentrations. Elevated EE concentrations increase the incidence of oral contraceptive-related adverse events, such as the risk of venous thromboembolism in women.
Hormone replacement therapy: simultaneous use of 120mg of this product and hormone replacement therapy containing conjugated estrogen (0.625mg Premel) for 28 consecutive days can make non-conjugated estrone, maleestrone and 17--estradiol The average steady-state AUC ₀ _24hr increased by 41%, 76%, and 22%, respectively. The long-term recommended dosage of this product (60mg and 90mg) and its combined use have not been studied. The effect of 120mg of this product on these estrogen AUC ₀ _24hr is less than half of that of Premel when taken alone and the dose increased from 0.625 to 1.25mg. The clinical significance of these elevated indicators is not clear, and the use of higher doses of Premarin in combination with this product has not been studied. When choosing postmenopausal hormone replacement therapy with this product, it is necessary to consider the increase in estrogen concentration.
Others -In the study of drug interactions, this product has no clinically significant effect on the pharmacokinetics of prednisone / prednisolone or digoxin. Antacids and ketoconazole (CYP3A4 strong inhibitors) have no clinically significant effect on the pharmacokinetics of this product.

Etoricoxib overdose

In clinical trials, single doses of up to 500 mg of this product and multiple doses of up to 150 mg / day were given for 21 consecutive days without significant toxic effects. Although adverse events have not been reported in most cases, acute overdose of this product has been reported. The most commonly observed adverse events are related to the safety aspects of this product (for example, gastrointestinal events, renal vascular events).
If an overdose occurs, conventional support measures can be taken, such as removing unabsorbed drugs from the gastrointestinal tract, giving clinical monitoring, and using supportive treatment if necessary.
This product cannot be removed by hemodialysis, and it is unclear whether it can be removed by peritoneal dialysis.

Cortisol Pharmacology and Toxicology

Pharmacological action

Etoricoxib is a non-steroidal anti-inflammatory drug that has anti-inflammatory, analgesic, and antipyretic effects in animal models. Within the clinical dose range or higher, this product is an orally active, selective cyclooxygenase-2 inhibitor. Two subtypes of cyclooxygenase have been identified: cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). COX-1 is involved in normal physiological functions mediated by prostaglandins, such as gastric mucosal cell protection and platelet aggregation. Non-selective non-steroidal anti-inflammatory drugs inhibit the production of COX-1, which can cause gastric mucosal damage and weaken platelet aggregation. COX-2 is mainly involved in the production of prostaglandins, which can cause pain, inflammation and fever. Etoxicus is a selective inhibitor of cyclooxygenase-2, which can reduce these symptoms and signs, reduce gastrointestinal side effects without affecting platelet function.

According to clinical pharmacological studies, the inhibitory effect on COX-2 appears to be dose-dependent within 150mg daily dose of this product, but has no inhibitory effect on COX-1.

In clinical trials, subjects received 120 mg (once a day), naproxen 500 mg (once twice a day), or placebo, respectively, to measure prostaglandin synthesis levels in gastric mucosal biopsy samples. Compared with placebo, this product does not inhibit prostaglandin synthesis in gastric mucosa, while naproxen inhibits prostaglandin synthesis in gastric mucosa by about 80%. These studies further support that this product is a selective inhibitor of COX-2.

Platelet function

In a multi-dose study, subjects took 150 mg of the product daily (for a total of 9 days), and bleeding time was not affected compared to placebo. A single dose of 250 mg or 500 mg also had no effect on bleeding time. In vivo studies have shown that at a dose of 150 mg, when plasma concentrations reach steady state, arachidonic acid or collagen-mediated platelet aggregation is not inhibited in vitro. These results are consistent with the COX-2 selectivity of this product.

Toxicology research

Genotoxicity : Retorcoxib has no genotoxicity and mutagenic effect.

Retorcoxib is secreted with the milk of lactating rats (see [Medication for pregnant and lactating women]).

Reproductive toxicity : Rat studies have shown that no developmental abnormalities were found when the dose was 15 mg / kg / day (the exposure was about 1.5 times the exposure when the human was taking 90 mg). In the rabbit test, a low incidence of cardiovascular malformations and increased post-implantation miscarriage was found when the drug exposure was approximately twice that when the drug was taken at 90 mg in humans. No dysplasia was found when the drug exposure was equivalent to or lower than that of 90 mg when taken in humans.

Carcinogenicity : Mice tests have not found that etoricoxib has carcinogenic effects. The rats were continuously administered for about 2 years, and the daily drug exposure was more than 6 times of the human clinical dose (90mg), and hepatocellular adenoma and thyroid follicular cell adenoma could occur.

Resoxid pharmacokinetics

According to foreign research reports:
absorb

Retorcoxib is well absorbed orally. The average oral bioavailability is close to 100%. When an adult takes 120 mg orally once a day on an empty stomach until steady state is reached, peak plasma concentrations occur after approximately 1 hour (T _max ) of administration (geometric mean C _max = 3.6 mcg / ml ). The geometric mean AUC ₀ _24hr is 37.8mcg.hr/ml. The pharmacokinetics of this product are linear in the clinical dose range.

If 120 mg of etoricoxib is taken daily, normal meals have no significant effect on the extent and rate of absorption. In clinical trials, meals are not taken into account when taking etoricoxib.

In 12 healthy subjects, whether administered alone or in combination with a magnesium hydroxide / aluminum antacid or in combination with a calcium carbonate antacid (having an acid neutralizing capacity of about 50 mEq), rely on pharmacokinetics Kinetics are similar (AUC is equivalent, C _{max is} within about 20%).
distributed

In the concentration range of recoxine from 0.05 to 5 mcg / ml, 92% bound to human plasma proteins. In the human body, the distribution volume (V _dss ) at steady state is about 120 liters.
Retorcoxib passes through the placenta of rats and rabbits, and the blood-brain barrier of rats.
metabolism

This product is completely metabolized, and the content of the original drug in the urine is less than 1%. The main metabolic pathway is catalyzed by cytochrome P450 (CYP) enzymes to form 6'-hydroxymethyl derivatives.

Five metabolites have been found in the human body. Its main metabolite is a 6'-carboxylic acid derivative, which is formed by further oxidation of a 6'-hydroxymethyl derivative. These major metabolites have either no detectable activity or only weak activity of cyclooxygenase-2 inhibitors. None of these metabolites inhibited cyclooxygenase-1.
Clear

In healthy individuals, a single dose of 25 mg of radiolabeled etoricoxib was administered intravenously. 70% of the radioactivity can be detected in urine, and 20% of the radioactivity can be detected in stool. Less than 2% of the drug is excreted in its original form.

Reliance on cortisol is almost always metabolized and then excreted by the kidneys. It was given 120 mg of etoricoxib once a day, and the steady-state concentration was reached within 7 days. The accumulation ratio is approximately 2 and the corresponding accumulation half-life is approximately 22 hours. Plasma clearance is approximately 50 ml / min.

Relying on coxima precautions

Clinical trials suggest that selective cyclooxygenase-2 inhibitors are at increased risk for thrombotic events, especially myocardial infarction and stroke, compared to placebo and some non-steroidal anti-inflammatory drugs (naproxen). Because the cardiovascular risk of selective cyclooxygenase-2 inhibitors may increase with higher doses and longer duration of medication, the duration of medication should be minimized and the lowest effective daily dose should be used. The patient's symptoms and response to treatment should be evaluated regularly.

Patients with significant risk factors for cardiovascular events (such as hypertension, hyperlipidemia, diabetes, smoking) or peripheral arterial disease should be carefully evaluated before receiving this product.

Doctors and patients should be alert to the occurrence of such events, even if they have no previous cardiovascular symptoms. Patients should be informed of the symptoms and / or signs of severe cardiovascular safety and the steps to be taken if they occur.

Patients should be alert to symptoms and signs such as chest pain, shortness of breath, weakness, and vague speech, and should seek medical help immediately after any of these symptoms or signs occur.

Because selective cyclooxygenase-2 inhibitors have no effect on platelets, such drugs cannot be used in place of aspirin for the prevention of cardiovascular disease. This product is one of these drugs and cannot inhibit platelet aggregation, so it cannot stop antiplatelet therapy.

Avoid combination with any other NSAID or aspirin.

Gastrointestinal adverse events (gastrointestinal ulcers or other gastrointestinal Increased risk of complications). There are currently no long-term clinical trials to fully evaluate and compare the safety of selective cyclooxygenase-2 inhibitors in combination with aspirin and non-steroidal anti-inflammatory drugs in combination with aspirin in the gastrointestinal tract.

It is not recommended for patients with advanced kidney disease. Patients with creatinine clearance <30ml / min have very limited clinical experience with this product. If it is necessary to begin the treatment of these patients with this product, it is recommended to closely monitor the patient's renal function.

Prolonged use of non-steroidal anti-inflammatory drugs can lead to renal papillary necrosis and other kidney damage. Prostaglandins secreted by the kidney may play a compensatory role in maintaining renal perfusion. Therefore, when renal perfusion is impaired, the use of this product can lead to a decrease in prostaglandin production, which in turn reduces renal blood flow, thereby impairing renal function. Patients most likely to have this reaction include patients who already have significant renal insufficiency, decompensated heart failure, or cirrhosis. Consider monitoring renal function in these patients.

This product should be used with caution in patients with obvious signs of dehydration. It is recommended to add water before starting treatment with this product.

As with other drugs known to inhibit prostaglandin synthesis, some patients experience fluid retention, edema, and hypertension after taking this product. The use of this product in patients with pre-existing edema, hypertension or heart failure should consider the possibility of fluid retention, edema or hypertension. All non-steroidal anti-inflammatory drugs (NSAIDs), including etoricoxib, are associated with new and recurrent congestive heart failure (see Adverse Reactions). Especially at high doses, taking this product may be more frequent and more severe than users of other non-steroidal anti-inflammatory drugs and selective cyclooxygenase-2 inhibitors. Therefore, it is necessary to take special care during the treatment of this product. Pay attention to blood pressure monitoring. If blood pressure rises significantly, other treatments must be considered.

Adverse reactions to gastrointestinal bleeding, ulcers, and perforations can occur at any time during treatment with all non-steroidal anti-inflammatory drugs, and the risks can be fatal. These adverse reactions may be accompanied by or without warning symptoms, regardless of whether the patient has a history of gastrointestinal adverse reactions or a history of severe gastrointestinal events. Physicians should be aware that some patients may develop upper gastrointestinal (GI) ulcer / ulcer complications that are not related to treatment. Although the risk of gastrointestinal toxicity of etoricoxib is not ruled out, the results of the MEDAL project show that the risk of gastrointestinal toxicity of patients taking etoricoxib 60 mg or 90 mg once daily is significantly lower than that of diclofenac sodium 150 mg per day. In a clinical study comparing ibuprofen and naproxen, patients taking this product once a day at 120 mg were at risk of developing upper gastrointestinal ulcers detectable by endoscopy than non-selective nonsteroidal anti-inflammatory drugs. Patients with inflammatory drugs were lower, but higher than the placebo group. Upper gastrointestinal ulcer / ulcer complications occur in patients treated with this product. These events can occur at any time of use without any warning signs. In addition to treatment factors, patients with a previous history of gastrointestinal perforation, ulcers and bleeding (PUB), including patients with a history of ulcerative colitis, Crohn's disease, and patients older than 65 years of age are at higher risk of developing PUB. Use with caution to avoid deterioration of the condition.

Clinical trials have shown that about 1% of patients taking 60 mg and 90 mg of this product for one year have experienced an increase in alanine aminotransferase and / or aspartate aminotransferase (approximately three times the upper limit of normal values). In clinical trials comparing active drugs, the incidence of aspartate aminotransferase and / or alanine aminotransferase elevations in patients treated with this product at 60 and 90 mg daily is similar to that in the naproxen-treated 1000 mg daily group. The incidence was significantly lower than that of the diclofenac 150 mg group. Elevated aspartate aminotransferase and / or alanine aminotransferase can be recovered in patients treated with this product, and about 50% of patients return to normal aspartate aminotransferase and / or alanine aminotransferase under continuous treatment.

Patients whose symptoms and / or signs suggest abnormal liver function, or whose liver function is abnormal through chemical verification, should be assessed for persistent abnormal liver function. If liver function continues to be abnormal (3 times the upper limit of normal value), this product should be discontinued.

Appropriate monitoring should be maintained in elderly people taking etoxicept and patients with kidney, liver or heart dysfunction. If exacerbations occur during treatment, appropriate measures should be taken, including termination of treatment.

Post-market surveillance reports of severe skin reactions associated with the use of non-steroidal anti-inflammatory drugs and certain selective cyclooxygenase-2 inhibitors, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrosis Some of the fatal reactions (see [Adverse Reactions]), including release-type rubella, are extremely rare. These serious events can occur without any warning. Patients are at highest risk for the following reactions early in the treatment period: most cases occur during the first month of treatment. Serious hypersensitivity reactions (such as allergic reactions and angioedema) have been reported in patients receiving etoricoxib (see [Adverse Reactions]). Certain selective cyclooxygenase-2 inhibitors can increase the risk of skin reactions in patients with a history of drug allergy. Retorcoxib should be discontinued at the first appearance of a rash, mucosal injury, or any other allergy.

In addition, this product can mask the signs of infection-fever. Special attention should be paid when applying this product to patients undergoing anti-infective treatment ^[3] .

Cortisol storage

Store below 30 ° C (86 ° F). Store in its original packaging.