Diclofenac, 50 mg, enteric-coated tablets, 20 pcs., NIZHFARM JSC buy in Moscow at a low price

Diclofenac, 20 pcs., 50 mg, enteric-coated tablets

In order to reduce the risk of adverse events, the drug should be used at the lowest effective dose for the shortest period necessary to relieve symptoms.

Therapy with NSAIDs, including diclofenac, particularly long-term and high-dose therapy, may be associated with a small increased risk of serious cardiovascular thrombotic events (including myocardial infarction and stroke).

In patients with significant risk factors for cardiovascular events (eg hypertension, hyperlipoproteinemia, diabetes mellitus and smoking), treatment with diclofenac-containing products should only be initiated after careful evaluation and analysis.

Because of the important role of prostaglandins in maintaining renal blood flow, special caution should be exercised when prescribing the drug to patients with cardiac or renal failure, hypertension, elderly patients, patients taking diuretics or other drugs that affect renal function, and patients with For some reason, there is a decrease in circulating blood volume (for example, after extensive surgery). If diclofenac is prescribed in such cases, monitoring of renal function is recommended as a precaution. After cessation of drug therapy, normalization of renal function indicators to initial values is usually observed.

When using diclofenac, phenomena such as bleeding or ulceration/perforation of the gastrointestinal tract, in some cases fatal, were observed. These phenomena may occur at any time when using the drug in patients with or without previous symptoms and a history of serious gastrointestinal diseases. In elderly patients, such complications can have serious consequences. If patients receiving diclofenac develop bleeding or ulceration of the gastrointestinal tract, the drug should be discontinued. To reduce the risk of toxic effects on the gastrointestinal tract, the drug should be used in the minimum effective dose for the shortest possible time, especially for patients with gastrointestinal ulcers. especially complicated by bleeding or perforation in history, as well as elderly patients.

Patients with an increased risk of developing gastrointestinal complications, as well as those receiving therapy with low doses of acetylsalicylic acid or other drugs that can increase the risk of damage to the gastrointestinal tract, should take gastroprotectors.

Patients with a history of gastrointestinal disorders, especially the elderly, should report all symptoms of the digestive system to their doctor.

When carrying out long-term therapy, it is necessary to monitor liver function, peripheral blood patterns, and stool analysis for occult blood.

With long-term use of diclofenac, there may be an increase in the activity of one or more liver enzymes. If liver dysfunction persists or progresses or signs of liver disease or other symptoms occur (for example, eosinophilia, rash, etc.), the drug should be discontinued. It should be borne in mind that hepatitis during the use of diclofenac can develop without prodromal phenomena.

Caution must be exercised when using diclofenac in patients with hepatic porphyria, since the drug can provoke attacks of porphyria.

Diclofenac can reversibly inhibit platelet aggregation, therefore, in patients with hemostasis disorders with long-term use, careful monitoring of relevant laboratory parameters is necessary.

In patients with bronchial asthma, seasonal allergic rhinitis, swelling of the nasal mucosa (including nasal polyps), chronic obstructive pulmonary disease, chronic respiratory tract infections (especially those associated with allergic rhinitis-like symptoms), as well as in patients with allergies to other medications (rash, itching, urticaria) when prescribing diclofenac, special care should be taken (preparedness for resuscitation measures).

Severe, in some cases fatal, skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, have been very rarely reported with the use of diclofenac. The highest risk and incidence of severe dermatological reactions were observed in the first month of treatment with diclofenac. If patients receiving the drug develop the first signs of skin rash, damage to the mucous membranes or other symptoms of hypersensitivity, diclofenac should be discontinued.

The anti-inflammatory effect of NSAIDs, including diclofenac, may complicate the diagnosis of infectious processes.

Due to the negative effect on fertility, the drug is not recommended for women planning pregnancy. In patients with infertility (including those undergoing examination), it is recommended to discontinue the drug.

Diclofenac 25 mg/ml 3 ml ampoules 10 pcs. solution for intramuscular administration in Moscow

Hypersensitivity to diclofenac or to any other drug from the group of non-steroidal anti-inflammatory drugs (NSAIDs), as well as to any of the excipients of the drug; erosive and ulcerative lesions of the gastrointestinal tract (in the acute phase), bleeding from the gastrointestinal tract, inflammatory bowel diseases (nonspecific ulcerative colitis, Crohn's disease); severe liver failure, liver disease in the acute period;
severe renal failure (creatinine clearance less than 30 ml/min), hyperkalemia;
complete or incomplete acetylsalicylic acid intolerance syndrome (rhinosinusitis, urticaria, nasal polyps, bronchial asthma that occurs when taking acetylsalicylic acid or other NSAIDs);
hematopoietic disorders, hemostasis disorders (including hemophilia);
pregnancy, breastfeeding period,
children under 18 years of age;
period after coronary artery bypass surgery;
with an increased risk of arterial thrombosis and thromboembolism;
chronic heart failure, functional class II-IV according to the NYHA classification;
clinically confirmed coronary heart disease;
diseases of peripheral arteries and cerebral vessels; uncontrolled arterial hypertension.

With caution:
coronary heart disease, cerebrovascular diseases, congestive heart failure, arterial hypertension, significant decrease in circulating blood volume (including after major surgery), edema syndrome, peripheral arterial disease, dyslipidemia, diabetes mellitus, anemia, bronchial asthma , renal failure (creatinine clearance less than 60 ml/min), alcoholism, erosive and ulcerative diseases of the gastrointestinal tract without exacerbation, history of liver disease, diverticulitis, condition after extensive surgery, inducible porphyria, old age, smoking, severe somatic diseases , systemic connective tissue diseases, long-term use of nonsteroidal anti-inflammatory drugs, simultaneous use of glucocorticosteroids, anticoagulants, antiplatelet agents, selective serotonin reuptake inhibitors, hyperlipidemia, the presence of
Helicobacter pylori infection.

Diclofenac – tablets, capsules, solution, suppositories, tablets

From the digestive organs. More often than 1% - abdominal pain or spasm, bloating, diarrhea, dyspepsia, nausea, constipation, flatulence, increased activity of liver transaminases, peptic ulcer, incl. with complications (perforation, bleeding), gastrointestinal bleeding without ulcer.

Less often than 1% - vomiting, jaundice, melena, blood in the stool, damage to the esophagus, aphthous stomatitis, dry mucous membranes (including the oral cavity), hepatitis, hepatonecrosis, cirrhosis, hepatorenal syndrome, changes in appetite, pancreatitis (including .ch. with concomitant hepatitis), colitis.

From the nervous system. More often than 1% - headache, dizziness.

Less often than 1% - sleep disturbance, drowsiness, depression, diplopia, anxiety, irritability, aseptic meningitis, convulsions, weakness.

From the senses. More often than 1% - tinnitus.

Less often than 1% - blurred visual perception, taste disturbance, hearing loss (including irreversible), scotoma.

From the side of the skin. More often than 1% - skin rash, itchy skin.

Less commonly 1% - alopecia, urticaria, eczema, toxic dermatitis, exudative erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), photosensitivity.

From the genitourinary system. More often than 1% is fluid retention.

Less often than 1% - nephrotic syndrome, proteinuria, oliguria, interstitial nephritis, papillary necrosis, acute renal failure, azotemia.

From the hematopoietic organs. Less often than 1% - anemia (including hemolytic and aplastic), leukopenia, thrombocytopenia, eosinophilia, agranulocytosis, thrombocytopenic purpura.

From the respiratory system. Less often than 1% - cough, bronchospasm, laryngeal edema.

From the SSS side. Less often than 1% - increased blood pressure, congestive heart failure.

Allergic reactions. Less often than 1% - swelling of the lips and tongue, anaphylactoid reactions, anaphylactic shock (usually develops rapidly).

Overdose.

Symptoms: dizziness, headache, hyperventilation, clouding of consciousness, in children - myoclonic convulsions, nausea, vomiting, abdominal pain, bleeding, impaired liver and kidney function.

Treatment: gastric lavage, activated charcoal, symptomatic therapy aimed at eliminating increased blood pressure, renal dysfunction, convulsions, gastrointestinal irritation, respiratory depression. Forced diuresis and hemodialysis are ineffective.

Indications for use

Diclofenac suppositories are used to relieve pain and prevent inflammatory processes in the presence of the following pathologies:

osteochondrosis;
osteoarthritis;
rheumatism;
arthritis;
spondyloarthritis;
sciatica;
migraine;
lovemago;
gout;
algodismenorrhea;
complications after injuries;
complications after operations;
ENT diseases (for example, laryngitis, otitis media).

Typically, the drug is taken in the form of tablets or ointments. But if oral administration is not possible (for example, in a weakened patient), the doctor prescribes rectal suppositories. This form of therapy has several advantages:

the gastric mucosa is not damaged;
the likelihood of developing muscle necrosis decreases;
no suppuration forms at the injection site;
more comfortable administration compared to injection.

Suppositories are used in combination treatment. For example, during the day the patient takes pills or receives an injection. At night, for a better therapeutic effect, suppositories are administered.

Suppositories are also used to treat prostatitis. In this case, the active substance does not enter the liver, but almost 100% goes to the affected prostate cells, which improves treatment results.

Another direction is in gynecology. Suppositories are placed in case of acute pain caused by inflammation of the ovaries or algomenorrhea. In this case, suppositories are inserted into the vagina, they dissolve quite quickly and actively affect the affected tissue.

Diclofenac Hemofarm retard Capsules, 20 pcs., 100 mg, for adults, film-coated

special instructions

In order to reduce the risk of adverse events, the drug should be used at the lowest effective dose for the shortest period necessary to relieve symptoms.
Therapy with NSAIDs, including diclofenac, particularly long-term and high-dose therapy, may be associated with a small increased risk of serious cardiovascular thrombotic events (including myocardial infarction and stroke).

When using diclofenac, phenomena such as bleeding or ulceration/perforation of the gastrointestinal tract, in some cases fatal, were observed. These phenomena may occur at any time when using the drug in patients with or without previous symptoms and a history of serious gastrointestinal diseases. In elderly patients, such complications can have serious consequences. If patients receiving diclofenac develop bleeding or ulceration of the gastrointestinal tract, the drug should be discontinued. To reduce the risk of toxic effects on the gastrointestinal tract, the drug should be used in the minimum effective dose for the shortest possible time, especially for patients with gastrointestinal ulcers, especially complicated by a history of bleeding or perforation, as well as elderly patients.

Patients with a history of gastrointestinal disorders, especially the elderly, should report all symptoms of the digestive system to their doctor.

When carrying out long-term therapy, it is necessary to monitor liver function, peripheral blood patterns, and stool analysis for occult blood.

Caution must be exercised when using diclofenac in patients with hepatic porphyria, since the drug can provoke attacks of porphyria. Diclofenac can reversibly inhibit platelet aggregation, therefore, in patients with hemostasis disorders with long-term use, careful monitoring of relevant laboratory parameters is necessary.

The anti-inflammatory effect of NSAIDs, including diclofenac, may complicate the diagnosis of infectious processes.

When taking 100 mg tablets, patients with diabetes should take into account the sucrose content in the drug (1 tablet contains 94.7880 mg of sucrose).

Contraindications and side effects

Suppositories and other forms of the drug are not used when the patient has certain contraindications:

individual intolerance to diclofenac or auxiliary components;
proctitis;
severe disorders of the kidneys, liver, heart.

Taking suppositories has virtually no contraindications, since the medicine is administered externally, without entering the stomach and other organs of the gastrointestinal tract. Therefore, this form of the drug, along with ointments and gel, can be considered the safest. Suppositories have practically no side effects. If the dosage is observed, they do not pose a health threat.

Diclofenac in the treatment of pain syndromes

The connection between pain and inflammation has been known since ancient times. And today, the most common medications for pain relief are drugs that have both anti-inflammatory and analgesic effects - non-steroidal anti-inflammatory drugs (NSAIDs).

History of the creation of diclofenac

The prototype of modern NSAIDs was acetylsalicylic acid, which was first synthesized by the young scientist Felix Hoffman at the end of the 19th century. The chemical structure and properties of acetylsalicylic acid became the guidelines by which new representatives of this class of medications were created (at first they were usually designated as “aspirin-like”). It is not so much the lack of effectiveness as the toxicity of high doses of acetylsalicylic acid that served as a powerful incentive for the development of new, “non-salicylate” NSAIDs. In 1966, during the implementation of a program to develop an anti-inflammatory drug with improved biological properties, more than 200 analogues of 0-aminoacetic acid were synthesized in a research laboratory to create a molecule with the necessary parameters, among which the most interesting results were shown by diclofenac sodium - the sodium salt of 0-[(2 ,6 dichlorophenyl)-amino]-phenyl-acetic acid.

Initially, diclofenac was used mainly in the treatment of rheumatological diseases, where both components are important: a pronounced anti-inflammatory and powerful analgesic effect, but subsequently, the scope of use of diclofenac expanded significantly. Currently, diclofenac is used in surgery, traumatology and sports medicine (for damage to the musculoskeletal system, damage to soft tissues (bruises, sprains), for postoperative pain relief), in neurology (for the treatment of back pain, tunnel syndromes, migraines), in gynecology for dysmenorrhea, adnexitis, in oncology as a means of the first stage of pain relief in the WHO ladder. Intramuscular administration of diclofenac sodium is an effective method of combating renal and hepatic colic. A special dosage form of diclofenac in the form of drops has found application in ophthalmology. General practitioners also prescribe diclofenac for various pain syndromes (Table 1).

Mechanism of action of diclofenac

The anti-pain effect of diclofenac is due to several mechanisms. The main mechanism of action of diclofenac is the suppression of cyclooxygenase (COX), an enzyme that regulates the conversion of arachidonic acid into prostaglandins, mediators of inflammation, pain, and fever [3].

Diclofenac and COX selectivity

In the early 90s of the twentieth century, two isoforms of the COX enzyme were discovered - COX-1 and COX-2. Most of the positive effects of NSAIDs (suppression of inflammation, pain, fever) are associated with inhibition of COX-2, and the development of adverse reactions (mainly in the form of damage to the gastrointestinal tract) is associated with suppression of COX-1 synthesis [4].

However, there are a number of exceptions to this rule. It has been shown that COX-1 may also play a role in the development of the inflammatory process. COX-1, together with COX-2, is produced by the synovium of patients with rheumatoid arthritis (RA) [5]. This is probably due to the lower effectiveness of selective COX-2 in some pain syndromes. Recent studies have found an increased risk of cardiovascular complications with the use of highly selective COX-2 inhibitors [6].

Diclofenac inhibits both COX isoenzymes, mostly COX-2. Inhibition of COX-1 by diclofenac is less compared to ibuprofen and naproxen, and therefore diclofenac is less likely to cause gastrointestinal damage. At the same time, inhibition of COX-1 (albeit less pronounced than that of non-selective NSAIDs) may explain the greater effectiveness of diclofenac compared to selective COX-2 inhibitors (meloxicam, celecoxib) in a situation where COX-1 is also involved in the pathogenesis of the disease ( for example, with RA). Inhibition of COX-2 by diclofenac is less than that of etoricoxib and rofecoxib, which reduces the risk of cardiovascular complications [6]. This balanced effect of diclofenac ensures high therapeutic activity with good tolerability of treatment.

Other mechanisms of the analgesic action of diclofenac

In addition to inhibition of prostaglandins, other mechanisms of action of diclofenac have been identified. An experimental study showed that diclofenac sodium can significantly inhibit the migration of leukocytes to the site of inflammation [7]. To a certain extent, diclofenac sodium can also affect the balance of cytokines, reducing the concentration of interleukin-6 and increasing the content of interleukin-10 [8]. This change in the ratio of these products helps slow down the secretion of anti-inflammatory factors. A decrease in the production of free oxygen radicals, which occurs under the influence of diclofenac sodium, can also help reduce the activity of the inflammatory process and limit its damaging effect on tissue [9].

In addition to pronounced anti-inflammatory activity, diclofenac sodium also has a powerful analgesic potential that is not related to its effect on inflammation [10]. It has a complex effect on various mechanisms of pain perception, providing effective suppression of pain of various etiologies. The drug has both central and peripheral antinociceptive effects.

The central analgesic activity of diclofenac sodium is mediated by opioid receptors, as evidenced by the fact that this effect is blocked by naloxone [11]. It appears to be associated with the effect of diclofenac sodium on tryptophan metabolism. After administration of the drug, the concentration of tryptophan metabolites in the brain, which can reduce the intensity of pain, significantly increases [12].

The local antinociceptive effect of diclofenac sodium appears to be associated not only with the suppression of prostaglandin synthesis, since in several experimental models of pain, local use of prostaglandin synthesis inhibitors such as indomethacin and celecoxib, unlike diclofenac sodium, did not achieve a significant analgesic effect [ 13]. The peripheral analgesic effect of diclofenac sodium is not associated with the opioid effect, since it is not eliminated by naloxone. At the same time, the use of compounds that block the formation of NO and the activation of guanylate cyclase suppressed the analgesic effect of diclofenac sodium. Inhibitors of various types of potassium channels also produced a similar effect [13–16]. In a culture of rat cerebellar cells, diclofenac sodium increased the activity of potassium channels, increasing the release of potassium from the cell [17]. These results suggest that the peripheral antinociceptive effect of diclofenac sodium may be associated with activation of several types of potassium channels involving NO and guanosine cyclomonophosphate (cyclo-GMP).

Thus, the analgesic effect of diclofenac may be due to its effect on various levels and links in the pathogenesis of pain. In addition to the analgesic effect associated with a decrease in inflammation in the damaged area due to inhibition of prostaglandins (COX-1 and COX-2), diclofenac can reduce pain by reducing inflammation and through other mechanisms (restraining the migration of leukocytes to the site of inflammation, influencing the balance of cytokines) by affecting on potassium channels at the peripheral level, and also reduce the perception of pain through central mechanisms (by increasing the synthesis of the serotonin precursor (tryptophan) in brain tissue).

Indications for the use of diclofenac

Despite the wide range of currently existing NSAIDs and the creation in recent years of a new class of symptomatic anti-inflammatory drugs (selective COX-2 inhibitors), diclofenac sodium remains the most popular drug among NSAIDs.

The use of diclofenac in rheumatology

From the very beginning of its appearance, diclofenac has found wide use in rheumatology. An important feature that allowed diclofenac to displace other drugs from the NSAID group that were used before was its high analgesic and analgesic activity, along with good tolerability.

The effect of diclofenac is manifested by a decrease in the duration of morning stiffness, a decrease in pain (at rest and during movement), a decrease in swelling, swelling of the joints, as well as an improvement in the functional ability of the joints, which helps to increase the range of movements. Diclofenac is the drug of choice for most rheumatological diseases; it is used to treat inflammatory and degenerative rheumatic diseases (arthritis, arthrosis, etc.).

The use of diclofenac in general medical practice, orthopedics, traumatology, sports medicine

The most common disorders in general medical practice are disorders of the musculoskeletal system. Pathology of the musculoskeletal system is diverse in etiology and pathogenesis. Pain in this group of lesions can be caused by trauma, degenerative processes, inflammation, dysplasia, and trophic changes (osteoporosis). The mechanisms of development of the disease can be inflammatory, mechanical, neurogenic, etc. The pronounced analgesic effect of diclofenac in moderate and severe pain, inflammatory processes that occur after operations and injuries, rapid relief of spontaneous pain and pain during movement, reduction of inflammatory edema at the wound site made this drug one of the most necessary for the treatment of disorders of the musculoskeletal system, which are found in general medical practice, orthopedics, traumatology, sports medicine, and neurology.

When treating orthopedic and traumatic injuries, the form of release of the drug is also important. The possibility of combining local and general forms of diclofenac allows you to achieve maximum effectiveness while minimizing possible side effects. Local forms of diclofenac are most widely used for diseases of extra-articular tissues (tenosynovitis, bursitis, rheumatic soft tissue lesions), injuries of tendons, ligaments, muscles and joints. General forms, such as tablets, suppositories, solutions for injections,? - for massive injuries (combined and combined injuries, postoperative conditions, head injuries, fractures of large bones, etc.).

The use of diclofenac in neurology

Diclofenac has found widespread use for the relief of pain syndromes in neurological practice. Diclofenac is indicated for the treatment of acute back pain, tunnel syndromes (carpal tunnel syndrome, cubital tunnel syndrome, etc.), and migraines.

The duration of use and method of administration of the drug depend on the intensity of the pain syndrome. For moderate pain syndromes that do not limit the patient’s motor capabilities, it is possible to apply gels and ointments containing diclofenac sodium to the painful areas (spasmodic muscles) for 7–10 days. In case of intense pain that significantly limits the patient’s movement within the premises, injection routes of administration of diclofenac sodium are used for 3–7 days with a subsequent transition to oral forms [18]. There are reports of higher effectiveness of phonophoresis with diclofenac compared to the use of ointment forms of the drug [19].

The use of diclofenac in gynecology

The ability to eliminate pain and reduce the severity of blood loss during primary dysmenorrhea allowed the use of diclofenac in gynecological practice [20]. For primary dysmenorrhea, the daily dose is selected individually; it is usually 50–150 mg. The initial dose should be 50–100 mg; if necessary, over several menstrual cycles it can be increased to 150 mg/day. Diclofenac should be started when the first symptoms appear. Depending on the dynamics of clinical symptoms, treatment can be continued for several days. Diclofenac can also be used for pelvic inflammatory diseases, including adnexitis.

Method of administration and dosage: which dosage form to choose?

The undoubted advantage of diclofenac is the variety of dosage forms, including tablets (fast and retarded action), solution for parenteral administration, suppositories, as well as forms used for local therapy: ointments, creams, gels, spray, which creates convenience in selecting an individual dose and method use of the drug in different patients. The ability to combine different routes of administration in the same patient reduces the risk of adverse reactions.

Diclofenac tablets

Tablet forms of diclofenac are available in various dosages (

). The dose and route of administration of the drug for each patient are determined individually, taking into account the severity of the disease. The average recommended dose for adults is 100–150 mg/day. The maximum daily dose of diclofenac is 200 mg. In relatively mild cases of the disease, as well as for long-term therapy, a daily dose of 75–100 mg is sufficient. The daily dose should be divided into several single doses. If it is necessary to treat night pain or morning stiffness, in addition to taking the drug during the day, you can prescribe diclofenac in the form of suppositories before bedtime; however, the daily dose should not exceed 150 mg. Once the clinical effect is achieved, the dose is reduced to the minimum maintenance dose.

Children aged 6 to 15 years (inclusive) are prescribed only 25 mg tablets. The daily dose is 0.5–2 mg/kg body weight (in 2–3 doses, depending on the severity of the disease).

Adolescents aged 16 to 18 years can be prescribed 50 mg tablets. The tablets should be taken with plenty of liquid, preferably before meals. The tablets should not be split or chewed.

Diclofenac in the form of delayed-release tablets

A special form of the drug is diclofenac in the form of prolonged-release tablets. As a result of the delayed release of the active substance when taking retarded forms of diclofenac sodium, the effect occurs later, but lasts longer. These pharmacokinetic features make it possible to achieve a reduction in the number of drug doses taken by patients (1–2 times a day instead of 3–4 times a day) while maintaining a stable high concentration of the drug at the site of inflammation. This makes it preferable to use diclofenac in a retarded form when long-term use of the drug is necessary (for chronic pain syndromes, mainly in rheumatological practice).

The recommended starting dose for adults is 75 mg, that is, 1 retard tablet per day. The same dose is used in relatively mild cases of the disease, as well as for long-term therapy. In cases where the symptoms of the disease are most pronounced at night or in the morning, it is advisable to prescribe retard tablets at night.

The tablets should be swallowed whole, preferably with meals. If it is necessary to increase the dose, use an additional 1-2 tablets of diclofenac 25 mg. The maximum daily dose is 200 mg.

Currently, the Swiss pharmaceutical company Sandoz produces 75 mg bilayer tablets, which are unique in that each tablet consists of two layers and includes 12.5 mg diclofenac sodium immediate release and 62.5 mg diclofenac sodium sustained release, which provides both rapid onset of action and prolonged action of the drug.

Children and adolescents under 18 years of age should not be prescribed retard tablets.

Diclofenac in the form of rectal suppositories

The dosage form of diclofenac in the form of suppositories has a number of advantages. Suppositories do not cause the complications that are possible with parenteral administration of drugs (the development of muscle necrosis, infiltrates and suppuration at the injection site). It is advisable to prescribe suppositories if it is impossible to take drugs by mouth (in weakened patients, in the presence of esophageal strictures, etc.). When taken orally, there is a direct damaging effect of diclofenac on the cells of the gastric mucosa. With other methods of administering the drug (suppositories, ointments), the risk of damage to the gastrointestinal tract remains, but it is significantly lower. That is why, if there are signs of damage to the stomach and duodenum, preference is given to suppository forms of diclofenac.

Very often, suppositories are used in combination therapy: during the day the patient receives either injections or tablets, and at night - suppositories, which creates a better therapeutic effect due to a more uniform and long-term maintenance of the concentration of the drug in the blood. In this case, the total daily dose of diclofenac should not exceed 150 mg.

Children aged 6 to 15 years (inclusive) are prescribed only 25 mg suppositories. The daily dose is 0.5–2 mg/kg body weight (the daily dose, depending on the severity of the disease, should be divided into 2–3 single doses). For the treatment of RA, the daily dose can be increased to a maximum of 3 mg/kg (in several administrations). Adolescents aged 16 to 18 years can also be prescribed 50 mg suppositories.

The suppository is inserted into the rectum, as deep as possible, preferably after preliminary cleansing of the intestines. Suppositories should not be cut into pieces, since such a change in the storage conditions of the drug may subsequently lead to disruption of the distribution of diclofenac.

Diclofenac in the form of solution for injection

Diclofenac in injection form is preferably used when a faster analgesic effect is needed, usually with more severe acute pain (renal or hepatic colic, acute pain associated with soft tissue injuries (bruise, sprain), acute back pain, postoperative pain .Usually 1 ampoule per day is prescribed, but in severe cases, 2 injections per day can be prescribed at intervals of several hours, alternating the sides of administration.The use of injections can be combined with other dosage forms of diclofenac.The duration of parenteral use should not exceed two days; treatment if necessary continue with the same diclofenac, but in the form of tablets or rectal suppositories. When used intramuscularly, the drug is injected deep into the upper outer quadrant of the buttock; no more than 2 ampoules (150 mg) of the drug are used during the day. For renal and hepatic colic, the administration of diclofenac is usually combined with the use of antispasmodics.In case of a pronounced muscular component of back pain, the administration of diclofenac is combined with the use of muscle relaxants.

Combinations of two or more NSAIDs should be avoided as their effectiveness remains unchanged and the risk of side effects increases.

Diclofenac in the form of products for external (local) use

The undesirable effect of NSAIDs on the body is sharply limited if they are used in the form of local applications. The dosage form for such therapy is a mixture of the active drug with a base that ensures absorption under the skin. This method of treatment allows you to inject the drug directly into the lesion. At the same time, the impact on other organs and tissues is minimal.

Abroad, there are dosage forms in the form of plates for gluing to the skin containing 1.3% diclofenac epolamine. Diclofenac in the form of wafers first appeared in Switzerland in 1993; currently, diclofenac in the form of wafers is registered in 43 countries around the world. Diclofenac tablets are intended primarily for those who cannot take the oral form of diclofenac due to contraindications. They are used for soft tissue damage (bruise, sprain, compression, osteoarthritis) provided that the integrity of the skin is maintained 2 times a day. The plates are convenient for use, but are more expensive than other dosage forms.

These drugs are convenient to use and easy to dose. After applying the drug to the skin, the active compound accumulates in regional soft tissues and no more than 6% of the active substance enters the bloodstream. Moreover, the content of the drug in the muscles in the application zone is approximately three times higher than its level in distant muscle tissue. This makes the use of gel forms of diclofenac preferable for a wide range of disorders of the musculoskeletal system. Gel forms of diclofenac are over-the-counter medications and are very popular.

Diclak gel is the only diclofenac preparation on the Russian market with a 5% maximum concentration of the active substance, which allows you to reduce the dose of the drug taken orally, and in some cases even replace tablets. Approved for use by children over 6 years of age.

Diclofenac as part of combination drugs for the treatment of pain

There are also dosage forms (ointments, gels) in which diclofenac is one of the main components. The combination of several drugs with different mechanisms of action can increase the effectiveness of treatment.

Safety

Diclofenac has an optimal combination of analgesic and anti-inflammatory effects and is well tolerated. Therefore, in the absence of contraindications, it can be used even for a long time. Studies have confirmed that treatment with diclofenac in fairly high doses (150 mg) with long-term use (up to 8 months or more) was well tolerated by patients [2]. Of course, diclofenac, like any NSAID, may have side effects and contraindications. However, it should be noted that side effects, among which ulceration of the gastrointestinal mucosa (GIT) should be primarily feared, develop more often in individuals with risk factors.

Risk factors for gastrointestinal tract damage include:

age over 65 years;
history of peptic ulcer;
eating food that increases gastric secretion (spicy, fatty, salty foods);
large doses or simultaneous use of several NSAIDs;
concomitant therapy with glucocorticoids;
female gender, since increased sensitivity of women to this group of drugs has been detected;
smoking;
drinking alcohol;
presence of Helicobacter pylori.

In this regard, treatment should begin with the lowest recommended dose, especially in risk groups. In individuals at risk, the daily dose of diclofenac should not exceed 100 mg; preference should be given to short-lived dosage forms of diclofenac and prescribed either 50 mg 2 times a day or 25 mg 4 times a day. Diclofenac should be taken after meals. When taking the drug for a long time, you should refrain from drinking alcohol, since diclofenac, like alcohol, is metabolized in the liver. If complaints from the gastrointestinal tract appear, it is necessary to perform esophagogastroduodenoscopy (EGD), and if you are systematically taking diclofenac, this procedure should be prescribed every 4-6 months, since NSAID gastropathy is often asymptomatic - “silent”.

If long-term use of diclofenac is necessary, which is especially important in rheumatology, it is advisable to prescribe diclofenac together with misoprostol, which protects the gastric mucosa from damage.

In patients with hypertension, it is necessary to monitor blood pressure levels; in patients with bronchial asthma, an exacerbation may occur while taking diclofenac. In patients with chronic liver and kidney diseases, small doses of the drug should be used, monitoring the level of liver enzymes.

Before prescribing diclofenac, the doctor must clarify whether the patient is taking any other medications due to concomitant diseases in order to avoid possible complications when using diclofenac in combination with other medications. It is known that diclofenac increases the plasma concentration of digoxin, lithium, cyclosporine A, including increasing its nephrotoxicity; increases the toxicity of methotrexate. Against the background of potassium-sparing diuretics, diclofenac increases the risk of hyperkalemia, and against the background of anticoagulants - the risk of bleeding. Diclofenac reduces the effect of diuretics, antihypertensives and hypnotics. Concomitant use of antidiabetic agents can lead to both hypo- and hyperkalemia.

More than 30 years have passed since the introduction of diclofenac into clinical practice. During this time, many new NSAIDs appeared. This has significantly expanded the ability to provide effective care to patients, since individual response to treatment is highly variable. However, diclofenac occupies a special place in this therapeutic arsenal. The combination of high efficiency, good tolerability and a variety of dosage forms of the drug make it possible to select the optimal therapy for a wide range of pain syndromes.

For questions regarding literature, please contact the editor.

A. B. Danilov , Doctor of Medical Sciences

FPPOV them. I. M. Sechenova, Moscow

Table 1. Indications for the use of diclofenac

Preparations for systemic use (tablets, injections, suppositories)

Rheumatology:

rheumatism;
RA, juvenile RA;
extra-articular forms of rheumatism, rheumatism of soft tissues - periarthritis, bursitis, tendovaginitis, fibrositis, myositis;
ankylosing spondylitis - ankylosing spondylitis;
osteoarthritis;
spondyloarthritis;
other mono- and polyarthritis;
degenerative joint diseases - arthrosis (coxarthrosis, spondyloarthrosis);
back pain associated with degenerative changes in the spine;
acute attack of gout

Neurology, traumatology, orthopedics, sports medicine, general medical practice:

dorsalgia (lumbago, sciatica, myofascial and muscle-tonic pain);
migraine and other types of headaches;
tunnel syndromes, other diseases accompanied by inflammation of non-rheumatic origin (neuralgia, neuritis, lumbar ischialgia, bursitis, capsulitis, synovitis, tendinitis or tenosynovitis);
traumatic bruises, sprains of ligaments, muscles and tendons; inflammatory swelling of soft tissues, muscle soreness (myalgia) and joints caused by heavy physical activity

Oncology:

drug of the 1st step of the WHO ladder for the treatment of pain due to cancer

General medical practice:

renal and biliary colic

Gynecology:

gynecological diseases accompanied by pain and inflammation (primary dysmenorrhea, adnexitis, etc.)

Traumatology, surgery, dentistry:

post-traumatic and postoperative pain syndromes;
obstetrics, gynecology, dental or other surgical procedures

Otorhinolaryngology:

for severe inflammatory diseases of the ear, nose and throat, which occur with severe pain, for example, pharyngitis, tonsillitis, otitis media. Treatment of the underlying disease is carried out in accordance with generally accepted principles, including the use of etiotropic therapy

Preparations for external and local use

Traumatology, sports medicine:

post-traumatic inflammation of soft tissues and the musculoskeletal system (tendons, ligaments, muscles and joints);
musculoskeletal injuries characteristic of sports medicine and sports: sprains, dislocations, bruises, contusions, overloads, etc.

Rheumatology:

local treatment of inflammatory and degenerative joint diseases: RA, osteochondrosis of peripheral joints and spine, periarthropathy, etc.

Rheumatology, neurology:

local treatment of inflammatory and degenerative diseases of soft tissues and periarticular tissues: tendovaginitis, shoulder-hand syndrome, bursitis, osteochondrosis, osteoarthrosis, periarthropathy, etc.;
arthralgia;
dorsalgia;
myalgia

Traumatology, surgery:

tenderness and inflammation of soft tissues

Ophthalmology:

non-infectious conjunctivitis, post-traumatic inflammation after penetrating and non-penetrating wounds of the eyeball, pain syndrome when using an excimer laser, during surgery for removal and implantation of the lens (pre- and postoperative prevention of miosis, cystoid edema of the optic nerve)

Table 2.

Instructions for use DICLOFENAC SODIUM

Suction

After intramuscular administration of 75 mg of diclofenac, its absorption begins immediately. Cmax in plasma, the average value of which is about 2.5 μg/ml (8 μmol/l), is reached after approximately 20 minutes. Immediately after its achievement, a rapid decrease in the concentration of the drug in plasma is observed. The amount of absorbed active substance is linearly dependent on the dose of the drug. The AUC value after intramuscular administration of the drug is approximately 2 times greater than after its oral or rectal administration, since in the latter cases, about half of the amount of diclofenac is metabolized during the “first pass” through the liver.

After repeated use of the drug, the pharmacokinetic parameters do not change.

Provided that the recommended intervals between administrations of the drug are observed, no accumulation is observed.

Distribution

Binding to serum proteins (mainly albumin) is 99.7%. The apparent Vd is 0.12-0.17 l/kg.

Diclofenac penetrates into the synovial fluid, where its Cmax is reached 2-4 hours later than in blood plasma. The apparent T1/2 from synovial fluid is 3-6 hours. 2 hours after reaching Cmax in plasma, the concentration of diclofenac in synovial fluid is higher than in plasma, and its values remain higher for a period of time up to 12 hours.

Metabolism

The metabolism of diclofenac is carried out partly by glucuronidation of the unchanged molecule, but mainly through single and multiple methoxylation, which leads to the formation of several phenolic metabolites (3′-hydroxy-, 4′-hydroxy-, 5′-hydroxy-, 4′,5 -dihydroxy- and 3′-hydroxy-4′-methoxydiclofenac), most of which are converted to glucuronide conjugates.

Two of these phenolic metabolites are biologically active, but to a significantly lesser extent than diclofenac.

Removal

The total systemic plasma clearance of diclofenac is 263±56 ml/min. The final T1/2 is 1-2 hours. T1/2 of 4 metabolites, including two pharmacologically active ones, is also short-lived and is 1-3 hours. One of the metabolites, 3′-hydroxy-4′-methoxy-diclofenac, has longer T1/2, however this metabolite is completely inactive. About 60% of the applied dose of the drug is excreted in the urine in the form of glucuronic conjugates of the unchanged active substance, as well as in the form of metabolites, most of which are glucuronic conjugates. Less than 1% of diclofenac is excreted unchanged. The remainder of the applied dose of the drug is excreted in the form of metabolites with bile and feces.

Pharmacokinetics in certain groups of patients

In patients with impaired renal function, when diclofenac sodium was prescribed in usual single doses, no accumulation of diclofenac was observed. If creatinine clearance is less than 10 ml/min, the calculated equilibrium concentrations of diclofenac hydroxymetabolites are approximately 4 times higher than in healthy patients. However, the metabolites are ultimately excreted in the bile.

In patients with chronic hepatitis or compensated liver cirrhosis, the pharmacokinetics of diclofenac are similar to those in patients without liver disease.