Instructions for use DIAFLEX
If concomitant use of antibiotics is necessary, which may disrupt the intestinal microflora, temporary cessation of therapy should be considered.
The risk/benefit ratio of treatment should be assessed in patients with a history of enterocolitis (especially in patients with irritable bowel syndrome).
Concomitant dietary intake increases the bioavailability of diacerein (about 24%), while significant dietary deficiency reduces bioavailability.
Taking diacerein often results in diarrhea, which can cause dehydration and hypokalemia. If diarrhea develops, the patient should stop taking the drug and contact their doctor immediately to discuss alternative treatment. Caution should be exercised if the patient is concomitantly receiving diuretics as Dehydration and hypokalemia may develop. Particular caution should be observed in case of hypokalemia in patients receiving cardiac glycosides (digitoxin, digoxin).
The simultaneous use of laxative drugs should be avoided.
Caution should be given to patients with renal impairment.
The drug contains lactose, so patients with rare hereditary diseases such as galactose intolerance, lapp lactase deficiency or glucose-galactose malabsorption syndrome should not take Diaflex.
During post-registration monitoring, cases of increased activity of liver enzymes in the blood serum and symptomatic acute liver damage were identified. Before starting treatment, the patient should be asked about concomitant, current and history of liver diseases, and an examination should be carried out to identify violations of the functional state of the liver. Liver diseases are a contraindication to the use of diacerein. It is necessary to monitor laboratory and clinical manifestations of liver damage, and observe precautions when used simultaneously with other drugs with the risk of developing hepatotoxic reactions. Treatment with diacerein should be discontinued if an increase in liver enzyme activity is detected or the development of symptoms of liver damage is suspected. The patient should be informed of the signs and symptoms of hepatotoxicity and advised to consult a physician immediately if symptoms of liver damage are suspected.
Patients should be advised to limit alcohol consumption while using diacerein.
Use in pediatrics
The safety and effectiveness of the drug in pediatric practice have not been established. The use of the drug in children and adolescents is not recommended due to lack of data.
Impact on the ability to drive vehicles and operate machinery
Data on the effect of the drug on the ability to drive vehicles and operate machinery are not provided.
Modern therapy of osteoarthritis
What are the main groups of drugs used in the treatment of osteoarthritis? What are the advantages of selective COX-2 inhibitors?
Osteoarthritis is a multifactorial chronic progressive disease, which is characterized by an imbalance between anabolic and catabolic processes, primarily in hyaline cartilage. In addition to hyaline cartilage in osteoarthritis, the pathological process involves the synovial membrane with the development of varying degrees of recurrent synovitis, as well as subchondral bone, articular capsule, intra-articular ligaments and periarticular muscles.
Osteoarthritis occurs at any age, but most often after 45-50 years. At the age of over 70 years, radiological signs of osteoarthritis are found in 90% of women and 80% of men, and in 20% of them osteoarthritis is clinically manifest. Pain and limited joint mobility caused by this disease sharply worsen the quality of life of patients and represent a serious socio-economic problem, being one of the main causes of disability.
The goal of drug therapy for osteoarthritis is to reduce and even completely stop pain in the joints and restore their functions, as well as prevent further progression of this disease by correcting impaired metabolism in hyaline cartilage. The drug therapy regimen for osteoarthritis includes two main classes of drugs:
- immediate action symptomatic drugs;
- drugs that structurally modify cartilage.
Second class drugs slow down the rate of progression of the disease, that is, they have a chondroprotective effect. Such medications primarily include structural analogues of cartilage tissue, namely the drug Dona (viartril, arthril, praxis, bioflex), the active ingredient of which is glucosamine sulfate, as well as the drug structum, which is chondroitin sulfate. These drugs modulate the essential functions of chondrocytes in osteoarthritis-damaged cartilage, stimulating the synthesis of sulfated and non-sulfated proteoglycans comparable to physiological proteoglycans, including their ability to form strong complexes with hyaluronic acid.
In addition to structum and don, second-class medications also include rumalon, which is an extract from cartilage tissue and bone marrow of calves; diacerin - interleukin-1 inhibitor; non-hydrolysable compounds from soy and avocado; hyaluronic acid preparations.
Many of the slow-acting drugs have not only chondroprotective, but also direct anti-inflammatory effects.
But still, non-steroidal anti-inflammatory drugs (NSAIDs) have the most striking anti-inflammatory effect, without which complex therapy for osteoarthritis is unthinkable [1, 2]. Their prescription is justified by the fact that, although osteoarthritis is a degenerative disease, manifestations of secondary synovitis or an inflammatory process in the periarticular soft tissues aggravate its progression. That is why the concept of “osteoarthritis” is accepted abroad. Drugs in this group are able to quickly reduce the intensity of pain in the affected joints, up to its complete relief, suppress exudative phenomena and restore range of motion, that is, actively influence the main subjective and objective symptoms of osteoarthritis. Many patients with this disease take NSAIDs almost constantly, since these are the only drugs that have a pronounced therapeutic effect and allow patients to maintain the ability to care for themselves.
Currently, several groups of NSAIDs are well known, pharmacokinetics have been studied in detail, indications for use, dosage regimens, and the range of possible adverse reactions have been clearly defined.
The main representatives of NSAIDs are derivatives of arylcarboxylic acids (aspirin, sodium salicylate, flufenamic and mefenamic acids), arylalkanoic acids (diclofenac, ibuprofen, flurbiprofen, naproxen, tolmetin, indomethacin, sulindac), enoliconic acid (phenylbutazone, piroxicam, meloxicam). The main mechanism of action of NSAIDs is the suppression of prostaglandin biosynthesis.
As is known, prostaglandins are characterized by a wide range of biological actions. They are mediators of inflammatory reactions and contribute to the development of edema and exudation, sensitize receptors to pain mediators (histamines and bradykinin), and also lower the threshold of pain sensitivity, increase the sensitivity of the hypothalamic centers to the action of pyrogens. Prostaglandins also regulate a large number of physiological processes, including intestinal motility, platelet aggregation, vascular tone, kidney function, gastric juice secretion, and trophism of the gastric mucosa. This makes it clear why NSAIDs have not only therapeutic anti-inflammatory, analgesic and antipyretic effects, but also numerous undesirable side effects.
The most common side effects are from the gastrointestinal tract (GIT), which manifest themselves in the form of gastric or intestinal dyspepsia, the formation of erosions and ulcers in the stomach and duodenum. Interestingly, in the United States, the number of deaths from gastrointestinal complications associated with traditional NSAIDs exceeds deaths from cervical cancer, bronchial asthma or melanoma.
The impetus for the development of new classes of NSAIDs with a smaller spectrum of side effects and good tolerability was the discovery in 1991 of two isoforms of cyclooxygenase (COX) - COX-1 and COX-2. Even earlier, J. Vane discovered that the anti-inflammatory effect of NSAIDs is associated with the suppression of COX, a key enzyme in the biosynthesis of prostaglandins. In 1995, the concept was put forward that COX-1 is a constitutive protective enzyme that has a cytoprotective effect and is naturally present in many tissues of the body, while COX-2 has pro-inflammatory activity and accumulates in high concentrations only in areas of inflammation. At the same time, it became clear that the side effects of NSAIDs are associated with inhibition of COX-1, and their anti-inflammatory effect is associated with inhibition of COX-2. Thus, the effectiveness and safety of NSAIDs are associated with selective suppression of COX-2 (b).
The modern pathogenetic classification of NSAIDs is based on their effect on individual COX isofermes. Thus, most NSAIDs used until recently (indole derivatives, diclofenac sodium, ibuprofen, piroxicam, etc.) are non-selective COX inhibitors. Meloxicam and nimesulide are COX-2 selective drugs. They have a certain anti-inflammatory effect at doses that inhibit COX-2 and yet cause significant inhibition of COX-1. A new class of specific COX-2 inhibitors includes celecoxib (Celebrex) and rofecoxib. As can be seen from the definition, specific COX-2 inhibitors act only on COX-2 and do not affect COX-1.
Celebrex was only accepted for clinical use in December 1998. This drug is the first specific COX-2 inhibitor specifically designed to reduce the number of adverse reactions (compared to other NSAIDs). The pharmacokinetic properties of Celebrex have been studied in healthy people. When taken orally, its maximum plasma concentration appears after 3 hours. 90% of the drug dose is metabolized in the liver and excreted in bile. The protein-binding capacity of this NSAID reaches 97%, and the half-life is 10-12 hours. The duration of action of Celebrex is 11 hours. The drug is poorly soluble in water and therefore is used only internally. Antacids reduce the bioavailability of the drug, and food intake increases it by 10-20%. Pharmacokinetics does not depend on age, which is especially important given the elderly age of patients with osteoarthritis. When treating osteoarthritis, the daily dose of Celebrex usually does not exceed 200-400 mg, but more often it is prescribed 200 mg once a day or 100 mg twice a day. It is best to take the drug with food, although the recommendations of the company that produces Celebrex indicate that its administration does not depend on food intake [4].
Placebo-controlled and comparative studies (with other NSAIDs) have shown the high therapeutic effectiveness of Celebrex in patients with osteoarthritis of the knee and hip joints. It turned out that this drug at a dose of 200 or 400 mg per day is comparable in its anti-inflammatory and analgesic activity to 1000 mg of naproxen, 150 mg of diclofenac or 2400 mg of ibuprofen. It had a positive effect on such indicators of the pathological process as the severity of joint pain, the severity and duration of morning stiffness, general disease activity assessed by the doctor and the patient, as well as the WOMAC index and the function of the affected joints. At the same time, the drug reliably changed their values [5]. In the vast majority of patients with secondary synovitis, resolution of exudative phenomena in the knee joints was observed.
In contrast to standard NSAIDs, which inhibit the synthesis of proteoglycans in arthritic cartilage and thereby further contribute to the progressive degeneration of cartilage, Celebrex has a chondroneutral effect, and possibly even prevents the lysis of chondrocytes and takes part in the repair of cartilage after damage. It follows from this that, if necessary, it can be used for a long time (for several weeks or even months) without any negative effect on the tissue of the affected joint.
Celebrex, which has the same therapeutic efficacy as other NSAIDs, is characterized by higher tolerability and safety of use. When taking the drug, it is possible to develop such side effects as abdominal pain, diarrhea, nausea, headache, dizziness, rhinitis, sinusitis. However, the incidence of these reactions is not statistically significant compared with placebo.
In cases of use of this drug for one week in high and ultra-high doses, according to endoscopic monitoring, no gastrointestinal toxicity was detected [3]. The incidence of gastric and duodenal ulcers with 200 mg Celebrex, 1000 mg naproxen, and 2400 mg ibuprofen administered continuously for three months was 7.5%, 36.4%, and 23.3%, respectively.
The use of specific COX-2 inhibitors in patients with osteoarthritis is also justified by the fact that they are compatible with other medicinal agents. This allows for adequate and timely treatment of concomitant diseases, which naturally occur in older people.
Literature
- Nasonov E. L. Specific inhibitors of cyclooxygenase-2 and inflammation: prospects for using the drug Celebrex // Russian Rheumatology. 1999. No. 4. pp. 1-8.
- Tsvetkova E. S. Modern pharmacotherapy of osteoarthritis // Consilium medicum. 1999. 1. C 205-206.
- Kaplan-Machlis B., Klostermeyer B., S. The cyclooxygenase-2 inhibitors: safety and effectiveness // Ann. Pharmacotherapy. 1999. 33: 979-988.
- Product information. Celebrex (celecoxib capsules). New York: Gd Searl and Co., 1998.
- Strand F. Efficacy of COX-2 specific inhibition in musculoskeletal pain and inflammation: clinical update. COX-2 specific inhibition. Satellite symposium at 2000 National Scene Mitting ACR. Philadelphia, 2000, 8.
- Vane JR, Botting RM The future of NSAID therapy: selective COX-2 inhibitors // Clinical Practice. 2000. 54: 7-9.
note
- Osteoarthritis is a multifactorial chronic progressive disease.
- The goal of drug therapy for osteoarthritis is to reduce or eliminate joint pain and restore joint function.
- The basis of therapy for osteoarthritis is drugs that structurally modify cartilage and NSAIDs
- The effectiveness and safety of NSAIDs is associated with selective inhibition of COX-2.
- Celebrex is the first specific COX-2 inhibitor.
