Celecoxib

Pharmacological properties

celecoxib is an oral cog-2 selective inhibitor in the clinical dosing range (200-400 mg / day). in healthy volunteers in this dosing range there was no statistically significant inhibition of cog-1 (which was evaluated as inhibition of ex vivo thromboxane b2 (txb2) formation).

COX is responsible for the formation of prostaglandins. Two of its isoforms were revealed: COX-1 and COX-2. COX-2 is an isoform of the enzyme that is induced by proinflammatory factors and is the main factor in the synthesis of prostanoid mediators of pain, inflammation and fever. COX-2 is also involved in the process of ovulation, implantation and closure of the ductus arteriosus, regulation of renal function and central nervous system (causes fever, sensation of pain, and cognitive function). It can also play a role in the healing of ulcers. COX-2 was detected in the tissues around a person’s stomach ulcers, but its significance for the healing of ulcers has not been established.

Differences in antiplatelet activity between some NSAIDs that inhibit COX-1 and selective COX-2 inhibitors may have clinical significance for patients at risk of thromboembolic reactions. Selective COX-2 inhibitors reduce the formation of systemic (and therefore, reliably, endothelial) prostacyclin without affecting platelet thromboxane.

Celecoxib - pyrazolam with substituted diaryl, is chemically similar to other non-arylamine sulfonamides (e.g. thiazides, furosemide), but differs from arylamine sulfonamides (e.g. sulfamethoxazole and other sulfonamide antibiotics).

After administration of high doses of celecoxib, a dose-dependent effect on the formation of TxB was noted₂. However, in healthy patients, in small studies of the use of reusable doses of 600 mg 2 times a day (3 times higher than the maximum recommended dose), celecoxib did not affect platelet aggregation and bleeding time compared with placebo.

Several studies have been conducted to confirm the effectiveness and safety of the drug in the treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis.

The use of celecoxib for the treatment of inflammation and pain in osteoarthritis of the knee and hip joint was evaluated in approximately 4,200 patients in studies controlled with a placebo and active drug for up to 12 weeks. The drug was also evaluated for the treatment of inflammation and pain in rheumatoid arthritis in approximately 2,100 patients in studies controlled with a placebo and active drug for up to 24 weeks. Daily doses of celecoxib 200-400 mg provided analgesia for 24 hours from the time of taking the drug. Celecoxib was evaluated for the symptomatic treatment of ankylosing spondylitis in 896 patients in studies controlled with placebo and an active drug for up to 12 weeks. Celecoxib at doses of 100 mg 2 times a day, 200 mg / day, 200 mg 2 times a day and 400 mg / day in these studies showed a significant decrease in the severity of pain, a decrease in the overall activity of the disease and improved functioning with ankylosing spondylitis.

Five randomized double-blind controlled trials were conducted, in which an endoscopic examination of the upper gastrointestinal tract was supposed to be performed, involving approximately 4,500 patients who did not have ulcers at the initial stage (celecoxib was prescribed in doses of 50-400 mg 2 times a day). In endoscopic studies lasting 12 weeks, celecoxib (at doses of 100-800 mg / day) represented a significantly lower risk of gastric and duodenal ulcers compared with naproxen (1000 mg / day) and ibuprofen (2400 mg / day). These data were not consistent when compared with diclofenac (150 mg / day).In two 12-week studies, the proportion of patients with gastric and duodenal ulcers detected by endoscopy did not significantly differ in patients who received placebo and celecoxib at doses of 200 and 400 mg 2 times a day.

In a prospective long-term safety study of long-term results (lasting from 6 to 15 months), 5800 patients with osteoarthritis and 2200 patients with rheumatoid arthritis received celecoxib at a dose of 400 mg 2 times a day (4 and 2 times higher than the doses recommended for osteoarthritis and rheumatoid arthritis ), ibuprofen 800 mg 3 times a day or diclofenac 75 mg 2 times a day (therapeutic doses for both drugs). 22% of participants took concomitant low doses of acetylsalicylic acid (325 mg / day) mainly for the prevention of cardiovascular disease. Relative to the main endpoint of a complicated ulcer (which was defined as gastrointestinal bleeding, perforation, or obstruction), celecoxib almost did not differ from ibuprofen or diclofenac. Also, for the pooled group that took NSAIDs, there was no statistically significant difference for complicated ulcers (relative risk (RR) 0.77; 95% confidence interval (CI) 0.41–1.46, based on the entire duration of the study). For the combined endpoint, complicated and symptomatic ulcers, the incidence was significantly lower in the group that received celecoxib compared to the group treated with NSAIDs (RR 0.66; 95% CI 0.45–0.97), but not between celecoxib and diclofenac. Patients who received celecoxib and concomitant low doses of acetylsalicylic acid were 4 times more likely to develop complicated ulcers compared to those who took celecoxib alone. The incidence of a clinically significant decrease in hemoglobin level (2 g / dl), confirmed by repeated analyzes, was significantly lower in patients who received celecoxib compared with the group who received NSAIDs (RR 0.29; 95% CI 0.17–0.48 ) Significantly lower the frequency of occurrence of this phenomenon when taking celecoxib persisted with the simultaneous use of acetylsalicylic acid, and without it.

In a prospective randomized 24-week safety study involving patients aged 60 years or with a history of stomach and duodenal ulcers (patients who took acetylsalicylic acid were excluded) the proportion of patients with a decrease in hemoglobin level (2 g / dl) and / or hematocrit (10%) due to confirmed or possible digestive disorders was lower in patients who received celecoxib at a dose of 200 mg 2 times a day (n = 2238), compared with patients, gender diclofenac SR at a dose of 75 mg 2 times a day + omeprazole at a dose of 20 mg 1 time per day (n = 2246) (0.2% compared with 1.1% for the etiology associated with disorders of the digestive tract, p = 0.004; 0.4% compared with 2.4% for a possible etiology associated with disorders of the digestive tract, p = 0.0001). The frequency of clinical manifestations of gastrointestinal complications, such as perforation, obstruction, or bleeding, was very low, and there were no differences between treatment groups (4–5 per group).

Cardiovascular safety - long-term studies involving patients with sporadic adenomatous polyps. Two studies of the use of celecoxib have been conducted, in which patients with sporadic adenomatous polyps took part. One study (study 1) recorded a dose-dependent increase in the combined endpoint — cardiovascular death, myocardial infarction, or stroke (confirmed) with celecosib compared with placebo over 3 years of treatment.Another study (study 2) did not demonstrate a statistically significant increase in the risk of having the same combined endpoint.

In the study, 1 RR compared to placebo for the combined endpoint (confirmed) - cardiovascular death, myocardial infarction, or stroke - was 3.4 (95% CI 1.4–8.5) with 400 mg celecoxib 2 times a day and 2.8 (95% CI 1.1–7.2) when using 200 mg celecoxib 2 times a day. The cumulative levels for this combined endpoint over a period of more than 3 years were 3.0% (20/671 patients) and 2.5% (17/685 patients), respectively, compared with 0.9% (6/679 patients) - for a placebo. The increase in values ​​for both groups that took celecoxib compared with placebo was mainly due to myocardial infarction.

In the study, 2 RR compared to placebo for the same combined endpoint (confirmed) was 1.2 (95% CI 0.6–2.4) with 400 mg celecoxib 1 time per day compared with placebo. The cumulative levels for this combined endpoint over a period of more than 3 years were 2.3% (21/933 patients) and 1.9% (12/628 patients), respectively. The incidence of myocardial infarction (confirmed) was 1.0% (9/933 patients) with 400 mg celecoxib once daily and 0.6% (4/628 patients) with placebo.

Data from a long-term study of the prevention of Alzheimers disease did not show a significant increase in cardiovascular risk when taking 200 mg of celecoxib 2 times a day compared with placebo. The RR compared with placebo for a similar combination point (cardiovascular death, myocardial infarction, or stroke) was 1.14 (95% CI 0.61–2.12) with 200 mg celecoxib 2 times a day. The frequency of myocardial infarction was 1.1% (8/717 patients) when taking 200 mg of celecoxib 2 times a day and 1.2% (13/1070 patients) when using placebo.

Pharmacokinetics Celecoxib is well absorbed, C_max it in plasma is reached after approximately 2-3 hours. Reception with food (high in fat) delays absorption by about 1 hour.

Celecoxib is excreted mainly through metabolism. Unchanged with urine, less than 1% of the dose is excreted. Individual variability of celecoxib exposure parameters may vary 10 times. In the therapeutic dose range, celecoxib demonstrates pharmacokinetics independent of dose and time. Binding to blood plasma proteins is about 97% at therapeutic plasma concentrations; the drug practically does not bind to red blood cells. T_½ is 8-12 hours. The equilibrium concentration in the blood plasma is achieved within 5 days of treatment. Pharmacological activity is inherent in the parent drug. The main metabolites detected in the blood did not have activity against COX-1 and COX-2, which could be determined.

Celecoxib is metabolized mainly with the participation of cytochrome P450 2C9. Three of its metabolites detected in human blood plasma (primary alcohol, the corresponding carboxylic acid and glucuronide conjugate) are inactive with respect to inhibition of COX-1 and COX-2.

The activity of cytochrome P450 2C9 is reduced in individuals with a genetic polymorphism, which leads to a decrease in the activity of this enzyme, for example, in individuals with a homozygous polymorphism of the CYP 2C9 * 3 enzyme.

In a pharmacokinetic study of the use of 200 mg celecoxib once a day by healthy volunteers genotyped as CYP 2C9 * 1 / * 1, CYP 2C9 * 1 / * 3 or CYP 2C9 * 3 / * 3, median C_max and AUC_0-24 celecoxib on day 7 was almost 4 and 7 times higher in patients genotyped as CYP 2C9 * 3 / * 3, compared with other genotypes. In three separate single-dose studies, in which only 5 patients genotyped as CYP 2C9 * 3 / * 3 took part, the AUC value_0–24 a single dose was almost 3 times higher than that in patients with normal metabolism. It was established that the homozygote of the * 3 / * 3 genotype is noted with a frequency of 0.3–1% among different ethnic groups.

The use of celecoxib in patients with known or expected decreased activity of CYP 2C9, which is based on a previous history / experience with the use of other CYP 2C9 substrates, should be carried out carefully.

There were no clinically significant differences in the pharmacokinetic parameters of celecoxib between elderly patients of the Negroid race and the Caucasian race.

Plasma concentrations of celecoxib increase by almost 100% in older women (65 years).

Compared to patients with normal liver function, patients with mild hepatic impairment_max celecoxib rises by an average of 53%, and the AUC value by 26%. In patients with moderate impaired liver function, these indicators are 41 and 146%, respectively. Metabolic ability in patients with mild to moderate impaired liver function was best correlated with their albumin scores. In patients with mild to moderate impaired hepatic function (with a serum albumin level of 25–35 g / l), treatment should begin with half the recommended dose. Patients with severe hepatic impairment (serum albumin 25 g / l) did not participate in the studies, therefore celecoxib is contraindicated in this group of patients.

The experience with celecoxib in patients with impaired renal function is negligible. The pharmacokinetics of celecoxib has not been studied in patients with impaired renal function, but it is unlikely that it will change significantly. Therefore, caution is required when treating patients with impaired renal function. The use of the drug in severe renal impairment is contraindicated.

Indications

Symptomatic treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis.

Application

Osteoarthrosis. the usual recommended daily dose is 200 mg in 1–2 doses. in some patients, in case of insufficient reduction in the severity of symptoms, increasing the dose to 200 mg 2 times a day can increase effectiveness. if within 2 weeks the therapeutic effect does not increase, other treatment options should be considered.

Rheumatoid arthritis. The recommended initial daily dose is 200 mg, distributed in 2 doses. If necessary, later this dose can be increased to 200 mg 2 times a day. If within 2 weeks the therapeutic effect does not increase, other treatment options should be considered.

Ankylosing spondylitis. The recommended daily dose is 200 mg in 1–2 doses. In some patients, if the severity of symptoms is not sufficiently reduced, increasing the dose to 400 mg in 1–2 doses may increase the effectiveness. If within 2 weeks the therapeutic effect does not increase, other treatment options should be considered.

The maximum recommended daily dose is 400 mg for all indications.

Rancelex capsules can be used regardless of food intake.

Elderly patients (65 years old): as in adult young patients, treatment should be started with a dose of 200 mg / day. If necessary, later this dose can be increased to 200 mg 2 times a day. With extreme caution, it is necessary to prescribe the drug to elderly patients with a body weight of 50 kg.

Impaired liver function: in patients with a diagnosed moderate impaired liver function and serum albumin level of 25–35 g / l, treatment should be started with half the recommended dose. Experience with this category of patients is limited to use in patients with cirrhosis.

Impaired renal function: experience with celecosib in patients with mild or moderate impaired renal function is limited, so treat these patients with caution.

Patients with a reduced CYP 2C9 metabolism: celecoxib should be used with caution in patients with a known or expected decrease in CYP 2C9 activity, which is based on the determination of the genotype or previous history / experience of using other CYP 2C9 substrates, since there is a risk of developing dose-related side effects.In such patients, half of the lowest recommended dose should be used at the beginning of treatment.

Contraindications

• The presence in the history of hypersensitivity to the active substance or any other component of the drug. known hypersensitivity to sulfonamides. active peptic ulcer or bleeding from the digestive tract. ba, acute rhinitis, nasal polyps, angioedema, urticaria or other allergic reactions after taking acetylsalicylic acid or NSAIDs, including cog-2 inhibitors, in history. use in women of reproductive age who do not use an effective method of contraception. severe liver dysfunction (serum albumin level 25 g / l or child-based assessment - I drink ≥10). severe renal impairment (established creatinine clearance of 30 ml / min). inflammatory bowel disease. congestive heart failure (class ii – iv according to nyha criteria). diagnosed with coronary artery disease, peripheral artery disease and / or cerebrovascular disease.

Side effects

Adverse reactions are indicated by classes of organ systems and frequency of development, displaying data obtained from the sources below.

Adverse reactions reported in patients with osteoarthritis and rheumatoid arthritis with a frequency higher than 0.01% and more often than with placebo during 12 controlled (using a placebo or active comparison drug) clinical trials lasting up to 12 weeks with celecoxib in doses of 100-800 mg. In additional studies using non-selective NSAIDs (comparison drugs), about 7400 patients with arthritis received celecoxib treatment at doses up to 800 mg, including approximately 2300 patients who had been treated for 1 year or longer. Adverse reactions that were observed with celecoxib in these additional studies were similar to those that occurred in patients with osteoarthritis and rheumatoid arthritis, are listed below.

Adverse reactions, the development of which was reported more often than with placebo, in patients receiving celecoxib at a dose of 400 mg / day in long-term studies of the prevention of polyp formation for up to 3 years.

Adverse reactions received during post-marketing observation as spontaneous messages during the period when more than 70 million people took celecoxib (in different doses, for different periods of time and for different indications). Since not all adverse events were reported, and they were not included in the safety databases, the frequency of occurrence of these reactions cannot be reliably determined.

The frequency of adverse reactions: very often (≥1 / 10), often (≥1 / 100, 1/10), infrequently (≥1 / 1000, 1/100), rarely (≥1 / 10,000, 1/1000) , with an unknown frequency (post-marketing experience *).

* Adverse reactions reported spontaneously and entered into safety monitoring databases over a period when more than 70 million people have used celecoxib (in different doses, over different periods and for different indications). As a result, the frequency of occurrence of these reactions cannot be reliably determined. Adverse reactions that occurred in the population that was observed during the post-marketing period are only those that were not indicated in studies regarding the treatment of arthritis or the prevention of polyps.

Infections and infestations: often - sinusitis, upper respiratory tract infection, urinary tract infection.

On the part of the blood and lymphatic system: infrequently - anemia; rarely - leukopenia, thrombocytopenia; unknown frequency - pancytopenia.

On the part of the immune system: often - worsening of the course of allergies; unknown frequency - severe allergic reactions, anaphylactic shock, anaphylaxis.

Metabolic disorders: infrequently - hyperkalemia.

Mental disorders: often - insomnia; infrequently - anxiety, depression, fatigue; rarely - confusion; unknown frequency - hallucinations.

From the nervous system: often - dizziness, hypertension; infrequently - paresthesia, drowsiness, cerebral infarction¹; rarely - ataxia, a change in taste; unknown frequency - headache, worsening with epilepsy, aseptic meningitis, ageusia, anosmia, intracranial hemorrhage with a fatal outcome.

From the side of the organ of vision: infrequently - blurred vision; unknown frequency - conjunctivitis, eye hemorrhage, occlusion of arteries or retinal veins.

From the side of the hearing organ: infrequently - tinnitus, hypoacusia¹.

From the cardiovascular system: very often - AH¹; often - myocardial infarction¹; infrequently - heart failure, palpitations, tachycardia, increased severity of hypertension; unknown frequency - artimia, hot flashes, vasculitis, pulmonary embolism.

From the respiratory system: often - pharyngitis, rhinitis, cough, dyspnea¹; unknown frequency - bronchospasm.

From the digestive system: often - abdominal pain, diarrhea, dyspepsia, flatulence, vomiting¹dysphagia¹; infrequently - constipation, belching, gastritis, stomatitis, aggravation of the inflammatory disease of the digestive tract; rarely - an ulcer of the duodenum, stomach, esophagus, small and large intestine, intestinal perforation, inflammation of the esophagus, melena, pancreatitis; unknown frequency - nausea, gastrointestinal bleeding, colitis / worsening colitis.

From the hepatobiliary system: infrequently - impaired liver function, increased ASAT and ALAT; rarely - increased levels of liver enzymes; unknown frequency - liver failure (in some cases with a fatal outcome or the need for liver transplantation), fulminant hepatitis (in some cases with a fatal outcome), liver necrosis, hepatitis, jaundice.

On the part of the skin: often - rash, itching; infrequently - urticaria; rarely - alopecia, photosensitivity; unknown frequency - ecchymosis, bullous rashes, exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema, acute generalized exanthematous pustulosis.

From the musculoskeletal system: infrequently - cramps of the lower extremities; unknown frequency - arthralgia, myositis.

From the urinary system: infrequently - increased creatinine, increased blood urea nitrogen; unknown frequency - acute renal failure, interstitial nephritis, hyponatremia.

From the reproductive system and mammary glands: the frequency is unknown - menstrual irregularities (not specified).

Common disorders: often - flu-like symptoms, peripheral edema / fluid retention.

¹Side effects that were noted during studies of the prevention of the formation of polyps with the participation of patients receiving celecoxib at a dose of 400 mg / day in two clinical trials lasting up to 3 years. Concerning studies of polyp formation prevention, only those side effects that were previously noted during post-marketing observation or developed much more often than in arthritis studies are listed above.

In addition, the following previously unknown adverse reactions that developed in patients receiving celecoxib at a dose of 400 mg / day in two clinical trials lasting up to 3 years were revealed during polyp prevention prophylaxis studies. Often - angina pectoris, irritable bowel syndrome, nephrolithiasis, increased levels of creatinine in the blood, benign prostatic hyperplasia, weight gain.Infrequently - infections caused by Helicobacter pylori, herpes zoster, erysipelas, bronchopneumonia, labyrinthitis, gum infection, lipoma, floating clouding of the vitreous body, conjunctival hemorrhages, deep vein thrombosis, dysphonia, hemorrhoidal defecation, gastritis, defecation, dermatitis, , nocturia, vaginal bleeding, tenderness of the mammary glands, fracture of the lower limb, increased sodium levels in the blood.

In the final data (considered) obtained as a result of studies on the prevention of the formation of polyps, with the participation of patients receiving celecoxib at a dose of 400 mg / day for a period of up to 3 years, the excess coefficient relative to placebo for myocardial infarction was 7.6 cases per 1000 patients ( infrequently), and for a stroke (type not specified), there was no excess coefficient relative to placebo.

special instructions

In patients using celecoxib, complications from the upper digestive tract (perforation, ulcers or bleeding) were observed, in some cases with a fatal outcome. it is recommended to use the drug with caution in patients with a high risk of gastrointestinal complications in the treatment of NSAIDs: elderly patients, patients who simultaneously take any other NSAIDs or acetylsalicylic acid, or patients with a history of gastrointestinal diseases such as ulcers and gastrointestinal intestinal bleeding.

There is a further increase in the risk of side effects of celecoxib from the gastrointestinal tract (gastrointestinal ulcer or other complications from the gastrointestinal tract) with the simultaneous use of celecoxib and acetylsalicylic acid (even at low doses). In long-term clinical studies, a significant difference in gastrointestinal tract safety between selective COX-2 inhibitors and acetylsalicylic acid compared with other NSAIDs and acetylsalicylic acid has not been proven.

The simultaneous use of celecoxib and non-aspirin NSAIDs should be avoided.

In lengthy placebo-controlled studies involving patients with sporadic adenomatous polyps who received celecoxib at doses of 200 mg 2 times a day or 400 mg 2 times a day, a greater number of severe cardiovascular events, mainly myocardial infarction, were observed compared with placebo.

Since the risks to the cardiovascular system due to taking celecoxib increase with the dose and duration of treatment, the shortest possible courses of therapy and the minimum effective doses should be used. It is necessary to periodically reevaluate the patients need for symptom relief and response to therapy, especially in patients with osteoarthritis.

Patients with significant risk factors for cardiovascular events (e.g., hypertension, hyperlipidemia, diabetes mellitus and smokers) should be given celecoxib only after a thorough assessment. Selective COX-2 inhibitors do not replace acetylsalicylic acid in the prevention of cardiovascular thromboembolic diseases, since they do not have antiplatelet properties. Therefore, antiplatelet therapy should not be discontinued.

As with other drugs that can inhibit prostaglandin synthesis, fluid retention and edema were observed in patients taking celecoxib. Therefore, celecoxib should be used with caution in patients who have a history of heart failure, left ventricular dysfunction or hypertension, as well as in patients with existing edema for any other reason, since inhibition of prostaglandins can lead to impaired renal function and fluid retention. It is also necessary to prescribe treatment with caution to patients who take diuretics or have other reasons for the development of hypovolemia.

Like all NSAIDs, celecoxib can lead to the development of hypertension or worsen the course of an existing hypertension, as well as increase the incidence of cardiovascular complications. It is necessary to carefully control blood pressure at the beginning of celecoxib administration and throughout the course of treatment.

Impaired renal or liver function, and especially impaired heart function, can develop with great certainty in elderly patients, therefore, during treatment with celecoxib, they should be under constant medical supervision.

Celecoxib, like other NSAIDs, can be toxic to the kidneys. In clinical studies using celecoxib, it was demonstrated that this drug affected the kidneys in the same way as NSAIDs were compared. Patients with impaired renal function, heart failure, liver dysfunction, as well as elderly patients are at increased risk of developing renal toxicity. The condition of such patients during treatment with celecoxib should be constantly monitored.

When taking celecoxib, the development of severe liver reactions was reported, including fulminant hepatitis (in some cases, fatal), liver necrosis and liver failure (in some cases, fatal or with liver transplantation). In cases where the time before the onset of the reaction was indicated, most severe adverse reactions from the liver developed within 1 month after the initiation of celecoxib therapy.

If during the treatment the patient worsens the function of any organ system indicated above, appropriate measures must be taken and the possibility of celecoxib treatment discontinued.

Celecoxib inhibits CYP 2D6. Although celecoxib is not a potent inhibitor of this enzyme, it may be necessary to reduce the dose of drugs whose dose is titrated individually and which are metabolized using CYP 2D6.

Patients with a weak metabolism of CYP 2C9 should be carefully treated.

Very rarely, serious skin reactions have been reported with celecoxib (some fatal), including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis. The highest risk of developing these reactions threatens patients at the initial stage of treatment: most of these cases were observed during the 1st month of therapy. Serious hypersensitivity reactions (anaphylactic shock and angioedema) have been reported in patients who received celecoxib. The highest risk of serious skin reactions or hypersensitivity reactions in patients with a history of sulfonamide allergies or allergic reactions to any other drug. Celecoxib needs to be canceled at the first manifestations of skin rashes, damage to the mucous membrane, or other manifestations of hypersensitivity.

Celecoxib may mask fever and other signs of inflammation.

Patients who use warfarin at the same time have experienced severe bleeding. It is necessary to prescribe with caution the combined treatment of celecoxib and warfarin or other anticoagulants for oral administration.

The drug contains lactose. Patients with rare hereditary diseases, such as galactose intolerance, lactase deficiency, or glucose-galactose malabsorption, should not be taken Rancelex.

Use during pregnancy and lactation. There are no clinical data regarding the use of celecoxib for the treatment of pregnant women. The potential risk to humans during pregnancy is unknown, but cannot be ruled out.Celecoxib, like other drugs that inhibit prostaglandin synthesis, can suppress uterine contractility and cause premature closure of the ductus arteriosus in the fetus during the last trimester of pregnancy. Celecoxib is contraindicated during pregnancy and women who are planning a pregnancy. If a woman becomes pregnant during treatment, celecoxib must be discontinued.

When celecoxib was used by a small number of women during breastfeeding, it was found that celecoxib is very low in breast milk. Women who use celecoxib need to stop breastfeeding.

Children. Do not use.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. Patients who experience dizziness, vertigo, or drowsiness during the use of celecoxib should refrain from driving vehicles or working with other mechanisms.

Interactions

Pharmacodynamic interactions

In patients who receive warfarin or other anticoagulants, anticoagulant activity should be monitored especially closely during the first days of celecoxib administration or during a change in its dose, as these patients have an increased risk of bleeding. Therefore, in patients who take oral anticoagulants, prothrombin time and the international normalized ratio, often