Description of the drug DICLOFENAC-LF for systemic use
The dose is selected individually; it is recommended to use the drug in the minimum effective dose, with the shortest possible treatment period.
For oral and rectal use
Adults
When taken orally in the form of tablets of regular duration or rectally in the form of suppositories, the recommended initial dose is 100-150 mg/day. In relatively mild cases of the disease, as well as for long-term therapy, 75-100 mg/day is sufficient. The daily dose should be divided into several doses.
When taken in the form of extended-release tablets, the recommended initial dose is 100 mg 1 time / day. The same daily dose is used for moderately severe symptoms, 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 take extended-release tablets at night.
To relieve night pain or morning stiffness
in addition to taking the drug during the day, diclofenac is prescribed in the form of rectal suppositories before bedtime; in this case, the total daily dose should not exceed 150 mg.
With primary dysmenorrhea
the daily dose is selected individually; usually it is 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. The drug should be started when the first symptoms appear. Depending on the dynamics of clinical symptoms, treatment can be continued for several days.
In elderly patients (65 years and older)
no adjustment of the initial dose is required.
In weakened patients, patients with low body weight
It is recommended to adhere to the minimum dose.
The drug should be used with particular caution in patients with diseases of the cardiovascular system (including uncontrolled arterial hypertension) or a high risk of developing cardiovascular diseases
. If long-term therapy (more than 4 weeks) is necessary in such patients, the drug should be used in a daily dose not exceeding 100 mg.
Children aged 1 year and older
The drug is prescribed in a dose of 0.5-2 mg/kg body weight/day (in 2-3 doses, depending on the severity of the disease). For the treatment of rheumatoid arthritis
the daily dose can be maximally increased to 3 mg/kg (in several doses). The maximum daily dose is 150 mg.
The drug in the form of extended-release tablets should not be used in children and adolescents under the age of 18 years.
For parenteral use
Adults
Injected deep into the / m. Single dose - 75 mg. If necessary, repeated administration is possible, but not earlier than after 12 hours.
Duration of use is no more than 2 days, if necessary, then switch to oral or rectal use of diclofenac.
In severe cases (for example, with colic), as an exception, 2 injections of 75 mg each can be given, with an interval of several hours (the second injection should be carried out in the opposite gluteal region). Alternatively, IM administration once a day (75 mg) can be combined with diclofenac in other dosage forms (tablets, rectal suppositories), and the total daily dose should not exceed 150 mg.
For migraine attacks
Diclofenac is recommended to be administered as early as possible after the onset of an attack, IM at a dose of 75 mg, followed by the use of suppositories at a dose of up to 100 mg on the same day, if required. The total daily dose should not exceed 175 mg on the first day.
In elderly patients (65 years and older)
no adjustment of the initial dose is required. In weakened patients and patients with low body weight, it is recommended to adhere to the minimum dose.
The drug should be used with particular caution in patients with diseases of the cardiovascular system (including uncontrolled arterial hypertension) or a high risk of developing cardiovascular diseases
. If long-term therapy (more than 4 weeks) is necessary in such patients, the drug should be used in a daily dose not exceeding 100 mg.
Children and teenagers under 18 years of age
Diclofenac should not be used intramuscularly in children and adolescents under 18 years of age due to the difficulty of dosing the drug.
Diclofenac 25 mg/ml (solution)
The risk of adverse reactions when using diclofenac increases with increasing dose and duration of treatment. In order to reduce the risk of adverse events, the drug should be used at the minimum effective dose for the shortest period necessary to relieve symptoms. With regular use of the drug, the need for symptom relief, response to treatment should be periodically assessed and the dose adjusted in a timely manner.
Damage to the gastrointestinal tract
When using diclofenac, phenomena such as bleeding or ulceration/perforation of the gastrointestinal tract, in some cases with fatal outcome, were observed. These events may occur at any time when using drugs in patients with or without previous symptoms and a history of serious gastrointestinal diseases. In older patients, such complications can have serious consequences. If bleeding or gastrointestinal ulceration develops in patients receiving diclofenac, the drug should be discontinued.
To reduce the risk of toxic effects on the gastrointestinal tract in patients with gastrointestinal ulcers. especially with a history of complicated bleeding or perforation, as well as in elderly patients, the drug should be used in the minimum effective dose. Patients at increased risk of developing gastrointestinal complications, as well as patients receiving therapy with low doses of acetylsalicylic acid (Aspirin), should take gastroprotectors (proton pump inhibitors or misoprostol) or other medications to reduce the risk of unwanted effects on the gastrointestinal tract.
Patients with a history of gastrointestinal lesions, especially the elderly, should report all abdominal symptoms to the doctor.
Patients with bronchial asthma
Exacerbation of asthma (NSAID intolerance/NSAID-induced asthma), angioedema and urticaria are most often observed in patients with bronchial asthma, seasonal allergic rhinitis, nasal polyps, chronic obstructive pulmonary disease or chronic infectious diseases of the respiratory tract (especially those associated with allergic rhinitis). rhinitis-like symptoms). In this group of patients, as well as in patients with allergies to other drugs (rash, itching or urticaria), special caution should be observed when using diclofenac (preparedness for resuscitation measures).
Skin reactions
Serious dermatological reactions such as exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, in some cases fatal, have been reported very rarely 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 diclofenac develop the first signs of skin rash, damage to the mucous membranes or other symptoms of hypersensitivity, the drug should be discontinued.
In rare cases, anaphylactic/anaphylactoid reactions may develop in patients who are not allergic to diclofenac.
Effects on the liver
Since during the period of use of diclofenac there may be an increase in the activity of one or more liver enzymes, monitoring of liver function is indicated as a precautionary measure during long-term therapy with the drug. 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.
Effects on the kidneys
During therapy with diclofenac, it is recommended to monitor renal function in patients with hypertension, impaired cardiac or renal function, the elderly, patients receiving diuretics or other drugs that affect renal function, as well as in patients with a significant decrease in the volume of circulating blood plasma of any etiology, for example, in the period before and after major surgical interventions. After cessation of drug therapy, normalization of renal function indicators to initial values is usually observed.
Effects on the cardiovascular system
Therapy with NSAIDs, including diclofenac, particularly long-term therapy and high-dose therapy, may be associated with a small increase in the risk of serious cardiovascular thrombotic complications (including myocardial infarction and stroke).
Patients with cardiovascular disease and a high risk of developing cardiovascular disease (eg, hypertension, hyperlipidemia, diabetes mellitus, smokers) should be prescribed the drug only after careful consideration and used with extreme caution, at the lowest effective dose when the minimum possible duration of treatment, since the risk of thrombotic complications increases with increasing dose and duration of treatment. With long-term therapy (more than 4 weeks), the daily dose of diclofenac in such patients should not exceed 100 mg. The effectiveness of treatment and the patient's need for symptomatic therapy should be periodically assessed, especially in cases where its duration is more than 4 weeks.
The patient should be instructed to immediately seek medical attention if the first symptoms of thrombotic disorders (eg, chest pain, shortness of breath, weakness, speech disturbances) appear. Impact on the hematopoietic system
Diclofenac may temporarily inhibit platelet aggregation. Therefore, in patients with hemostasis disorders, it is necessary to carefully monitor relevant laboratory parameters. With long-term use of diclofenac, it is recommended to conduct regular clinical tests of peripheral blood.
Masking signs of an infectious process
The anti-inflammatory effect of diclofenac may complicate the diagnosis of infectious processes.
Use simultaneously with other NSAIDs
Diclofenac should not be used concomitantly with other NSAIDs, including selective COX-2 inhibitors, due to the risk of increased adverse events.
Impact on women's fertility
Diclofenac may have a negative effect on women's fertility, so diclofenac is not recommended for women wishing to become pregnant. In women experiencing difficulty conceiving (including those undergoing testing), the possibility of discontinuing the use of diclofenac should be considered.
The sodium metabisulfite contained in the drug can rarely cause severe hypersensitivity reactions and bronchospasm.
Information for Patients on a Sodium Controlled Diet
The sodium content in one ampoule (3 ml) of Diclofenac solution for injection does not exceed 1 mmol (23 mg), i.e. practically “sodium-free”.
Diclofenac and its various forms in the treatment of rheumatic diseases
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Considering the pronounced anti-inflammatory, analgesic, and cardioprotective activity of non-steroidal anti-inflammatory drugs (NSAIDs), the range of their use is growing every year.
This group of drugs is received by 20 to 40% of elderly people, with 6% of them receiving it for more than 9 months. Numerous works by domestic and foreign scientists draw attention to the fact that 7% of men and 12% of women take prescription forms of NSAIDs and almost 30% of patients take these medications without consulting a doctor. According to official statistics only, in Russia the overall incidence of musculoskeletal diseases over the past 10 years (1988–97) has increased from 7.7 million to 11.2 million
(that is, by more than 40%), and the real the prevalence of these diseases is likely much higher.
Nonsteroidal anti-inflammatory drugs (Table 1) are a class of pharmacological agents whose therapeutic activity is associated with preventing the development or reducing the intensity of inflammation through participation in the metabolism of arachidonic acid (Fig. 1).
Rice. 1. Metabolism of arachidonic acid
All “standard” NSAIDs have a number of characteristic chemical and pharmacological properties. Being weak organic acids, they have the ability to accumulate at the site of inflammation, where lower pH values are observed, and they are also well absorbed in the gastrointestinal tract, binding to albumin, and have approximately the same volume of distribution.
Discovered in 1971, diclofenac is today recognized as the “gold standard” of rheumatology.
, with which new drugs - selective NSAIDs - are also compared. Among the most effective NSAIDs, it seems to be the best in terms of its combination of pronounced anti-inflammatory and analgesic effects with satisfactory tolerability. The undoubted advantage of diclofenac is the variety of dosage forms, the rapid onset of analgesic and anti-inflammatory effects, and the possibility of combining oral and local forms.
Diclofenac is available in the form of tablets, dragees, short-acting and retarded capsules, solutions for intramuscular injection, rectal forms, as well as ointments, creams, and gels. It should be noted that the bioavailability of diclofenac when administered orally reaches 50%, and when administered locally - 6%, which dictates the need for 3-4 times application of the drug to the area of painful joints to achieve a pronounced anti-exudative, analgesic effect.
After ingestion of film-coated tablets, diclofenac is completely absorbed as they pass through the intestines. Although absorption occurs quickly, its onset may be delayed due to the presence of an enteric coating on the tablet. After a single dose of 50 mg of the drug, the maximum plasma concentration is observed after 2 hours and is 1.5 μg/ml (5 μmol/l). The degree of absorption is directly dependent on the dose.
If you take a tablet of the drug during or after a meal, its passage through the stomach slows down (compared to taking it on an empty stomach), but the amount of diclofenac absorbed does not change.
Since about 50% of diclofenac is metabolized during the first passage through the liver (“first pass effect”), the area under the concentration-time curve (AUC) when administered orally is almost half that of an equivalent dose parenterally. drug.
After repeated doses of the drug, the pharmacokinetics do not change. Therefore, if the recommended intervals between doses of the drug are observed, accumulation is not observed.
In children, the concentrations of diclofenac in the blood plasma when prescribed equivalent doses of the drug (mg/kg body weight) are similar to the corresponding indicators in adults.
After taking a retard tablet containing 100 mg of the active substance, the average value of its maximum plasma concentration is achieved on average after 4 hours and persists for 24 hours. Food intake does not have a clinically significant effect on the absorption of the active substance from retard tablets and its systemic bioavailability. The degree of absorption is directly dependent on the dose of the drug.
Absorption of diclofenac from rectal suppositories begins quickly, although the rate of absorption is somewhat slower than when taken orally with enteric-coated tablets. After using a rectal suppository containing 50 mg of the active substance, its maximum plasma concentration is achieved on average within 1 hour.
Diclofenac is metabolized partly by glucuronidation of the unchanged molecule, but mainly by single and multiple methoxylation, which leads to the formation of several phenolic metabolites, most of which are converted to glucuronide conjugates. Two of these phenolic metabolites are biologically active, but to a significantly lesser extent than diclofenac.
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 through bile and feces.
The average daily therapeutic dose is 150 mg. Increasing the dose to 200 mg per day is possible in rare cases and requires careful monitoring. After achieving a therapeutic effect, the dose should be reduced to 50–100 mg.
Along with rheumatic diseases, they are widely used for various pathological conditions characterized by acute and chronic pain, and also as a component of preoperative and postoperative analgesia (Table 2).
In addition to the listed indications, one of the points of application of diclofenac is dorsopathies.
The term “ dorsopathy
” refers to pain syndromes in the trunk and extremities of non-visceral etiology and associated with degenerative diseases of the spine, which are divided into 3 main groups: deforming dorsopathies, spondylopathies, and dorsalgia.
In the “spondylopathies” section, the most common degenerative changes include spondylosis, which includes arthrosis and degeneration of the facet joints (spondyloarthrosis). Spondyloarthrosis
is a type of osteoarthrosis with localization of the degenerative process in the intervertebral joints, which are ordinary synovial joints with two articular surfaces covered with hyaline cartilage, and is the most common cause of back pain.
Currently, the contribution of aseptic inflammation to the genesis of pain syndrome in dorsopathies has been studied, which requires the prescription of NSAIDs. Diclofenac and its analogues are prescribed for spondyloarthrosis as early as possible, but it is possible to use different treatment regimens. Typically, in the first 10 days, diclofenac is administered 3.0 ml intramuscularly 1-2 times a day, then switch to oral forms of 50 mg 3 times a day. In addition to tablets, rectal and gel forms of diclofenac, including combined ones, are used. Thus, an effective local therapy containing diclofenac, methyl salicylate, as well as menthol and a-linolenic acid, is Dicloran Plus
. The effectiveness of the drug is due to the synergistic effect of its constituent components:
- Diclofenac provides anti-inflammatory and analgesic effect;
- Methyl salicylate has a local warming and irritating effect;
- a-linolenic acid has an anti-inflammatory effect;
- Menthol causes vasodilation and increased local microcirculation, as well as an irritating (distracting) effect, creates a slight anesthetic effect, and enhances the absorption of diclofenac.
The maximum effect is achieved when applying a thin layer of the drug to the affected area of the skin 3 times a day. In some cases, the use of Dicloran Plus allows you to reduce the dose of oral NSAIDs and thus reduce the risk of damaging the mucous membrane of the gastrointestinal tract (GIT).
As is known, the damaging effect on the gastrointestinal mucosa is one of the main problems that arise when prescribing NSAIDs. Since 1987, the damaging effect of NSAIDs on the mucous membrane of the stomach and duodenum has been referred to as “ NSAID gastropathy.”
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NSAID gastropathy has been studied in sufficient detail, the main links of pathogenesis are known, and the possibilities of therapy and prevention have been clarified in serious clinical studies that meet the requirements of evidence-based medicine. Despite the undoubted ulcerogenic activity of NSAIDs, it is obvious that gastrointestinal complications are not a natural consequence of their use. Risk factors play a major role in the occurrence of NSAID gastropathy, so in these patients treatment should begin with taking COX-2 selective NSAIDs or “standard” NSAIDs in combination with preventive measures (Table 3). As preventive measures, proton pump inhibitors are used once a day (omeprazole 20 mg) with mandatory esophagogastroduodenoscopic examination once every 3–6 months.
If an ulcerative lesion of the gastrointestinal tract is detected, it is necessary to stop taking NSAIDs, if necessary, it is possible to use “simple” analgesics (paracetamol), then prescribe omeprazole 20 mg per day or ranitidine at a dose of 300 mg per day for 8 weeks with possible anti-Helicobacter therapy . The question remains open about the need for eradication therapy for NSAID gastropathy (Table 4). However, at the consensus conference on the problems of diagnosis and treatment of Helicobacter pylori
in Maastricht (September 21–22, 2000), a group of lesions of the upper gastrointestinal tract as a result of taking NSAIDs was classified as a possible indication for eradication therapy. The results of clinical studies on this problem are given in the form of separate provisions.
Thus, diclofenac is undoubtedly the drug of choice in the treatment of acute and chronic pain and inflammation. Extensive experience in use and a variety of dosage forms allow you to choose the optimal individual treatment regimen for each patient, and the use of Dicloran Plus significantly reduces the risk of side effects (effects on the gastrointestinal tract).