Celecoxib

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Celecoxib: instructions for use and reviews

1. Release form and composition
2. Pharmacological properties
3. Indications for use
4. Contraindications
5. Method of application and dosage
6. Side effects
7. Overdose
8. Special instructions
9. Application during pregnancy and lactation
10. Use in childhood
11. In case of impaired renal function
12. For violations of liver function
13. Use in the elderly
14. Drug interactions
15. Analogs
16. Terms and conditions of storage
17. Terms of dispensing from pharmacies
18. Reviews
19. Price in pharmacies

Latin name: Celecoxib

ATX code: M01AH01

Active ingredient: celecoxib (Celecoxib)

Manufacturer: JSC VERTEX (Russia)

Description and photo update: 2018-27-11

Prices in pharmacies: from 163 rubles.

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Celecoxib is a non-steroidal anti-inflammatory drug (NSAID).

Release form and composition

The drug is produced in the form of capsules: gelatinous solid, size No. 0, white (dosage 100 mg) and yellow (dosage 200 mg) color; the contents of the capsules are a compacted mass that disintegrates when lightly pressed, or a granular powder of almost white or white color (10 pcs. in a blister strip, in a cardboard box 1, 2, 3, 4, 5 or 10 packages; 10, 50 or 100 pcs. In a polyethylene can, in a cardboard box 1 can and instructions for the use of Celecoxib).

1 capsule contains:

active ingredient: celecoxib - 100 or 200 mg;
additional substances: sodium lauryl sulfate, lactose monohydrate, croscarmellose sodium, magnesium stearate, povidone K-30;
capsule shell: gelatin, titanium dioxide, additionally for 200 mg - yellow iron oxide (iron oxide).

Pharmacological properties

Pharmacodynamics

Celecoxib has analgesic, anti-inflammatory and antipyretic effects by inhibiting the production of inflammatory prostaglandins (Pg), mainly as a result of suppression of cyclooxygenase-2 (COX-2). The activation of COX-2 occurs as a result of the development of inflammation and leads to the production and accumulation of Pg, mainly PgE ₂, while the symptoms of inflammation (pain and edema) are increased. In humans, the drug in therapeutic doses does not lead to significant inhibition of cyclooxygenase-1 (COX-1) and does not affect the Pg produced as a result of COX-1 induction, and also does not affect the course of normal physiological processes associated with COX-1 in tissues. 1 (especially in the tissues of the intestines and stomach) and in platelets.

Active substance reduces excretion PgE ₂ and metabolite of prostacyclin - 6-keto-PgF ₁, but has no effect on the level of thromboxane B ₂ in the serum and urinary excretion of the metabolite thromboxane B ₂ - 11 degidrotromboksana In ₂ (both are products of the COX -1).

The glomerular filtration rate (GFR) in the elderly and patients with chronic renal failure (CRF) does not decrease as a result of the action of celecoxib, and sodium excretion also temporarily decreases. Against the background of arthritis, the incidence of arterial hypertension, heart failure and peripheral edema is comparable to that of treatment with nonselective COX inhibitors, which suppress the activity of COX-1 and COX-2. This effect was most pronounced in patients taking diuretics. Nevertheless, an increase in the incidence of increased blood pressure (BP) and the development of heart failure was not recorded, and the resulting peripheral edema was not severe and went away on its own.

Pharmacokinetics

Celecoxib is well absorbed after oral administration on an empty stomach. Its maximum concentration (C _max) in the blood plasma is observed after approximately 2-3 hours and with the introduction of 200 mg is 705 ng / ml. The absolute bioavailability of the substance has not been studied. The area under the concentration-time pharmacokinetic curve (AUC) and C _{max are} approximately proportional to the oral dose of celecoxib in a dose range of not more than 200 mg 2 times a day. If the agent is used in higher doses, the increase in AUC and C _max is less proportional.

The substance almost completely (97%) binds to plasma proteins, regardless of the level of its concentration and does not show a connection with blood erythrocytes. Passes through the blood-brain barrier.

Metabolic transformation occurs in the liver through hydroxylation, oxidation and, to some extent, glucuronidation. Metabolism is carried out mainly with the participation of the cytochrome P450 isoenzyme CYP2C9. The metabolites of celecoxib detected in the blood have no pharmacological activity in relation to COX-1 and COX-2. In individuals with homozygous for CYP2C9 * 3 polymorphism, the activity of cytochrome P450 CYP2C9 is reduced.

Celecoxib is excreted by the kidneys and through the intestines in the form of metabolites - 27 and 57%, respectively, less than 1% of the dose taken is excreted unchanged. After repeated administration, the half-life (T _1/2) is 8-12 hours, and the clearance is approximately 500 ml / min. Equilibrium plasma concentrations of the agent in repeated use are reached by the fifth day of therapy, the variability of such pharmacokinetic characteristics as C _max, AUC and T _{1/2 is} approximately 30%. In young healthy patients, the mean volume of distribution of celecoxib at steady state is approximately 500 L / 70 kg, indicating a wide distribution of the agent in tissues.

Food with a high fat content and taken together with the drug leads to an increase in its complete absorption by about 20%, and the time to reach C _max increases by 4 hours on average.

It has been found that the AUC in representatives of the Negroid race is approximately 40% higher than that in Europeans. The clinical significance and causes of this phenomenon are unknown.

Indications for use

rheumatoid arthritis, osteoarthritis, ankylosing spondylitis (symptomatic treatment);
pain syndrome, including back pain, postoperative, musculoskeletal and other types of pain;
primary dysmenorrhea.

Contraindications

Absolute:

severe cerebrovascular disease, severe peripheral arterial disease, clinically confirmed coronary artery disease (IHD);
subarachnoid hemorrhage, hemorrhagic stroke;
chronic heart failure (CHF) II – IV functional class according to NYHA classification (New York Association of Cardiology);
the period after coronary artery bypass grafting (in the first 10-14 days after the operation, the risk of cerebral circulation disorders and myocardial infarction is aggravated);
inflammatory bowel diseases (Crohn's disease, ulcerative colitis) during an exacerbation;
active erosive and ulcerative lesions of the gastric mucosa and / or duodenal ulcer, gastric ulcer and / or duodenal ulcer in the acute phase, gastrointestinal bleeding;
severe renal failure - creatinine clearance (CC) below 30 ml / min; confirmed hyperkalemia, progressive kidney disease;
severe liver failure;
aspirin triad: partial or complete combination of recurrent polyposis of the nose and paranasal sinuses, bronchial asthma and intolerance to acetylsalicylic acid or other NSAIDs, including other COX-2 inhibitors (including indications in history);
age up to 18 years;
pregnancy and lactation;
glucose-galactose malabsorption, lactase deficiency, lactose intolerance;
hypersensitivity to any of the constituents of the drug or sulfonamides.

Relative (treatment with Celecoxib should be performed with extreme caution):

lesions of the gastrointestinal tract (GIT), including gastric ulcer and 12 duodenal ulcer, Crohn's disease, ulcerative colitis, history of bleeding; presence of Helicobacter pylori infection;
CRF (CC 30-60 ml / min);
fluid retention and swelling;
a pronounced decrease in the volume of circulating blood (BCC), including after surgery;
arterial hypertension, diseases of the cardiovascular system (CVS); peripheral arterial disease;
cerebrovascular lesions;
liver dysfunctions of moderate severity, history of liver disease, hepatic porphyria;
diabetes mellitus, dyslipidemia / hyperlipidemia;
severe somatic diseases;
belonging to slow metabolizers or suspicions of such a condition (since these patients may accumulate celecoxib in blood plasma in high concentrations);
old age, as well as low body weight, a weakened body, diuretic treatment;
tuberculosis;
smoking and / or alcoholism;
long-term use of NSAIDs;
combined administration with inhibitors of the isoenzyme CYP2C9;
concomitant treatment with the following means: oral glucocorticosteroids (prednisolone), antiplatelet agents (clopidogrel, acetylsalicylic acid), anticoagulants (warfarin), selective serotonin reuptake inhibitors (paroxetine, fluoxetine, sertraline, citalopram.), digoxetine.

Celecoxib, instructions for use: method and dosage

Celecoxib is taken by mouth with water, with or without food. The capsule is swallowed whole without chewing, without opening.

Since the risk of complications from CVS is aggravated with an increase in the dose and duration of therapy, the drug should be taken in the lowest effective dose for the shortest possible course. With long-term use, the maximum daily dose should not exceed 400 mg.

Recommended dosage regimen:

symptomatic therapy of rheumatoid arthritis: 2 times a day, 100 or 200 mg;
symptomatic therapy of osteoarthritis / ankylosing spondylitis: 200 mg once a day or 100 mg twice a day; with ankylosing spondylitis, in some cases, the effectiveness of using the drug in a daily dose of 400 mg was noted;
pain syndrome / primary dysmenorrhea therapy: on the first day - an initial dose of 400 mg, if necessary, followed by an additional dose of 200 mg; from the second day of therapy - 200 mg 2 times a day, if necessary.

In patients with an established or suspected slowdown in metabolism (in carriers of the homozygous genotype CYP2C9 * 3), as well as in patients receiving treatment with fluconazole (an inhibitor of the CYP2C9 isoenzyme), the initial recommended dose of the drug should be halved.

Side effects

immune system: rarely - angioedema; extremely rarely - bullous rashes (bullous dermatitis);
blood and lymphatic system: infrequently - anemia; rarely, thrombocytopenia;
nervous system: often - dizziness; infrequently - increased muscle tone;
mental disorders: often - insomnia; infrequently - drowsiness, anxiety; rarely - confusion (psychosis);
sense organs: blurred vision, tinnitus;
CVS: often - increased blood pressure, including worsening of the course of arterial hypertension; peripheral edema; infrequently - palpitations, hot flashes, tachycardia, myocardial infarction and ischemic stroke;
hepatobiliary system: increased activity of liver enzymes, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST);
Gastrointestinal tract: often - flatulence, diarrhea, abdominal pain, dyspepsia, vomiting; infrequently - lesions of the teeth (postextraction alveolitis); rarely - ulceration of the esophagus, stomach ulcer and 12 duodenal ulcer; extremely rare - pancreatitis, intestinal perforation;
respiratory system, chest and mediastinal organs: often - cough, upper respiratory tract infections, sinusitis, bronchitis; infrequently - rhinitis, pharyngitis;
urinary system: often - urinary tract infections;
skin and subcutaneous tissues: often - skin rash, itching (including generalized); infrequently - ecchymosis, urticaria; rarely - alopecia;
general disorders: infrequently - accidental injuries, flu-like syndrome, facial edema, hypersensitivity.

Adverse reactions recorded in post-marketing observations:

immune system: extremely rare - anaphylactic reactions;
organ of vision: infrequently - conjunctivitis;
nervous system: extremely rare - loss of smell / taste, aseptic meningitis, cerebral hemorrhage;
mental disorders: rarely - hallucinations;
respiratory system, chest and mediastinal organs: rarely - pneumonitis, pulmonary embolism;
vascular system: extremely rare - vasculitis;
hepatobiliary system: rarely - hepatitis; extremely rarely - cholestasis, jaundice, cholestatic hepatitis, fulminant hepatitis (sometimes fatal), liver failure, liver necrosis (in some cases with fatal outcome or the need for liver transplantation); most of these reactions occurred 1 month after the start of the course of therapy;
Gastrointestinal tract: rarely - gastrointestinal bleeding;
reproductive system: rarely - menstrual irregularities; with an unknown frequency - decreased fertility in women;
skin and subcutaneous tissues: rarely - photosensitivity reactions; extremely rare - erythema multiforme, drug rash in combination with eosinophilia and systemic symptoms [DRESS syndrome (drug-induced hypersensitivity syndrome with eosinophilia) or hypersensitivity syndrome], toxic epidermal necrolysis, Stevens-Johnson syndrome, exfoliative dermatitis, acute generalized exanthematous;
urinary system: rarely - hyponatremia, acute renal failure; extremely rarely - lipoid nephrosis (disease of minimal changes), nephrotic syndrome, tubulointerstitial nephritis;
general disorders: infrequently - chest pain.

Overdose

Clinical experience with celecoxib overdose is limited. When using the drug in doses not exceeding 1.2 g once, or repeatedly 1.2 g, divided into 2 doses per day, clinically significant side effects were not observed.

If this condition is suspected, appropriate supportive therapy is prescribed. Given the high degree of binding of the substance to blood plasma proteins, it can be assumed that dialysis is not an effective method for its elimination from the body.

special instructions

Celecoxib, having an antipyretic effect, is able to reduce the diagnostic significance of such a symptom of an infectious lesion as fever, and thereby influence the diagnosis of infection.

The drug, like all coxibs, exacerbates the risk of serious side effects (including fatalities) from CVS, including thrombus formation, stroke and myocardial infarction. The threat of these complications may increase with an increase in the dose and duration of administration, as well as with existing CVS diseases and risk factors for such lesions. In order to minimize the potential threat of such reactions, Celecoxib should be used in the lowest effective doses for the shortest possible period of treatment (as recommended by the attending physician). It is required to take into account the likelihood of developing these complications even in the absence of the appearance in the past of symptoms of impaired cardiovascular activity. Patients should be informed about the signs of serious side effects from CVS and about the measures to be taken if they are observed.

Celecoxib can increase blood pressure, thus leading to the development of cardiovascular complications. In the presence of arterial hypertension, the drug should be used with caution, monitoring blood pressure readings at the beginning of the course and throughout the entire period of treatment.

During therapy with the drug, cases of ulceration, perforation and bleeding from the gastrointestinal tract were extremely rare. The factors that increase the risk of developing these complications during the treatment of NSAIDs include old age, the presence of cardiovascular diseases, concomitant intake of acetylsalicylic acid, bleeding, ulcers and inflammatory processes of the gastrointestinal tract during an exacerbation (including instructions in the history). In addition, the threat of bleeding from the gastrointestinal tract is aggravated by the combined use of oral anticoagulants and glucocorticosteroids, prolonged treatment with NSAIDs, alcohol consumption and smoking. The majority of serious gastrointestinal adverse reactions were observed in elderly and debilitated patients.

On the background of therapy, in very rare cases, the appearance of such severe skin side reactions as Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis was recorded. Some of them were fatal. The highest risk of these complications is observed in the first month of treatment. Celecoxib should be discontinued immediately if skin rashes, changes in mucous membranes or any other signs of hypersensitivity develop.

Influence on the ability to drive vehicles and complex mechanisms

During the use of the drug, special care should be taken when driving vehicles and working with complex and potentially dangerous equipment, since therapy can lead to dizziness and drowsiness.

Application during pregnancy and lactation

Taking the drug during pregnancy is contraindicated. The potential threat of treatment during pregnancy has not been identified, but cannot be ruled out. There have been no adequate studies on the use of celecoxib in pregnant women. In the treatment of NSAIDs (including celecoxib), according to the mechanism of action, some women may experience changes in the ovaries, causing impaired fertility or complications during pregnancy. Women planning a pregnancy or undergoing examination for infertility should consider the possibility of withdrawing NSAIDs.

The drugs obtained during pregnancy, especially in the third trimester, belonging to the group of Pg synthesis inhibitors, including celecoxib, can cause weak uterine contractions and premature closure of the ductus arteriosus in the fetus. The use of these drugs early in pregnancy can have a negative effect on its course.

During lactation, taking the drug is contraindicated. Studies have found that celecoxib is excreted in breast milk at very low concentrations. However, the possible risk of adverse effects in the breastfed baby must be considered.

Pediatric use

Celecoxib therapy is contraindicated in patients under the age of 18 years due to the lack of experience with its use in adolescents and children.

With impaired renal function

In elderly patients with a GFR value> 65 ml / min / 1.73 m ², due to age-related changes, and in patients with a GFR of 35-60 ml / min / 1.73 m ², the pharmacokinetic parameters of celecoxib do not change. There is also no significant relationship between the level of CC and drug clearance. In the presence of mild to moderate renal failure, dose adjustment is not necessary.

It is believed that severe renal failure does not affect the clearance of celecoxib, since the main route of its excretion is biotransformation in the liver with the formation of inactive metabolites. However, in patients with progressive kidney disease, severe renal failure (CC less than 30 ml / min) or confirmed hyperkalemia, due to the lack of experience with the use of the drug, its use is contraindicated.

For violations of liver function

It is contraindicated to use the drug in patients with severe hepatic impairment (class C according to the Child-Pugh classification) due to insufficient experience of its use in patients of this group.

In the presence of mild hepatic impairment (class A according to the Child-Pugh classification), the plasma concentration of celecoxib in the blood may slightly change, with moderate hepatic insufficiency (class B according to the Child-Pugh classification), it can increase almost 2 times, as a result of which it is required reduce the initial recommended dose by 2 times.

In patients with moderate hepatic impairment, hepatic porphyria, and a history of liver damage, treatment with Celecoxib should be performed with caution. When observing symptoms and / or signs of liver dysfunction, patients should be closely monitored to detect the possible occurrence of more severe liver reactions.

Use in the elderly

In persons over 65 years of age, the average values of AUC and C _{max of} celecoxib increased by 1.5-2 times, which is mainly due not to age, but to a change in body weight (in patients of this age category, as a rule, there is a lower average body weight, compared with young patients). As a result, they have higher levels of the substance. For this reason, women over 65 are more likely to have a higher plasma concentration of the active substance in the blood than older men.

Usually, elderly patients do not require dose adjustment, but if the patient's body weight is less than 50 kg, at the beginning of the course of therapy, it is advisable to take the minimum recommended dose.

Drug interactions

inhibitors of the isoenzyme CYP2C9: the level of celecoxib in the blood plasma increases, which requires a decrease in its dose;
fluconazole (an inhibitor of the isoenzyme CYP2C9): when used in a daily dose of 200 mg, it doubles the content of celecoxib in the blood plasma due to the suppression of its metabolism through the isoenzyme CYP2C9, and therefore it is required to reduce the dose of celecoxib by half;
barbiturates, carbamazepine, rifampicin (inducers of the isoenzyme CYP2C9): the plasma concentration of celecoxib in the blood decreases and its dose may need to be increased;
oral anticoagulants (including coumarin anticoagulants, warfarin, direct oral anticoagulants, including dabigatran, apixaban and rivaroxaban): there may be an increase in prothrombin time, as well as an increased risk of bleeding; after starting combination therapy or changing the dose of celecoxib, it is required to monitor anticoagulant activity and / or the indicator of the international normalized ratio (INR);
ketoconazole (an inhibitor of the CYP3A4 isoenzyme): no clinically significant effect on the biotransformation of celecoxib was observed;
metoprolol, dextromethorphan (substrates of the CYP2D6 isoenzyme): while taking the drug in a daily dose of 200 mg, the concentrations of metoprolol and dextromethorphan increase 1.5 and 2.6 times, respectively, due to the suppression of the activity of the CYP2D6 isoenzyme by celecoxib; at the beginning of the course of treatment with the drug, it is necessary to reduce the doses of drugs related to the substrates of the CYP2D6 isoenzyme, and after the completion of the course - to increase;
methotrexate: no clinically significant pharmacokinetic interactions were observed with this combination;
antihypertensive drugs, including angiotensin receptor blockers (angiotensin II antagonists), β-blockers, diuretics / angiotensin converting enzyme (ACE) inhibitors: the effect of these drugs decreases as a result of suppression of Pg production; in patients with impaired renal function or in elderly patients, dehydrated (including with concomitant diuretic therapy), the combined use of selective COX-2 inhibitors and other NSAIDs with angiotensin II antagonists, ACE inhibitors and diuretics can provoke deterioration of renal function, including development of acute renal failure, these effects are usually reversible; with such a combination, care must be taken and rehydration before starting celecoxib;at the beginning of combination therapy and periodically during its implementation, monitor kidney function;
lisinopril: according to studies, taking celecoxib twice a day at a dose of 200 mg during treatment with lisinopril in patients with grade I and II arterial hypertension did not cause a clinically significant increase in blood pressure when compared with the placebo group; 48% of study participants did not respond to treatment with lisinopril compared with patients taking placebo, in whom no response was noted in 27%;
thiazide diuretics, furosemide: a decrease in the natriuretic effect of these drugs is possible due to a decrease in renal Pg production;
cyclosporine: the risk of developing nephrotoxicity is aggravated due to the effect of NSAIDs on renal Pg synthesis;
oral contraceptives (norethisterone at a dose of 1 mg / ethinylestradiol at a dose of 0.035 mg): no significant effect on the pharmacokinetic parameters of the contraceptive combination was recorded;
other NSAIDs (not containing acetylsalicylic acid): this combination should be avoided;
lithium preparations: there was an increase in the plasma concentration of lithium by about 17%; patients receiving lithium treatment require careful monitoring when taking celecoxib or withdrawing it;
aluminum and magnesium-containing agents (antacids), glibenclamide, omeprazole, tolbutamide, phenytoin: no clinically significant interactions were observed;
acetylsalicylic acid (in low doses): there was no effect on the antiplatelet effect of this substance; Since celecoxib has a weak effect on platelet function, it should not be used as a substitute for acetylsalicylic acid, which is used to prevent cardiovascular lesions;
barbiturates (inducers of the isoenzyme CYP2C9): it is possible to reduce the plasma concentration of celecoxib in the blood, since it is metabolized in the liver by the isoenzyme CYP2C9;
digoxin: there is no information on this interaction, however, taking into account the effect of celecoxib on the CVS, it is required to combine it with caution with this substance, carefully controlling side reactions.

Analogs

Analogues of Celecoxib are: Roucoxib-Routek, Dilaxa, Celecoxib-Vial, Celebrex, etc.

Terms and conditions of storage

Store out of the reach of children and protected from light, at a temperature not exceeding 25 ° C.

Shelf life is 2 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Celecoxib

The few reviews of doctors and patients about Celecoxib are in most cases positive. Experts consider the drug to be an effective anti-inflammatory and analgesic drug that allows you to quickly achieve the desired result with a minimum of side reactions. The drug gently helps to cope with pain in the neck, lower back, chest, with irradiation of pain in the lower extremities. The advantages of the drug also include a convenient form of release and ease of use.

As the disadvantages of the drug, many patients indicate the appearance of undesirable effects against the background of its administration (dizziness, nausea, abdominal pain, vomiting).

Price for Celecoxib in pharmacies

The price for Celecoxib (200 mg capsules) can vary between 300-500 rubles. per package containing 10 pcs.

Celecoxib: prices in online pharmacies

Drug name

Price

Pharmacy

Celecoxib 200 mg capsule 10 pcs.

163 r

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Celecoxib capsules 200mg 10 pcs.

183 r

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Celecoxib capsules 200mg 30 pcs

426 r

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Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!