DICLONATE P
Side effects
Side effects are primarily dose dependent and vary widely among patients.
This is especially true for the risk of gastrointestinal bleeding (gastritis, erosion, ulcer), which largely depends on both the dose of the drug and the duration of treatment. The frequency of side effects is classified according to the recommendations of the World Health Organization: very often (> 1/10); often (from >1/100 to <1/10); uncommon (>1/1000 to <1/100); rare (from >1/10000 to <1/1000); very rare (<1/10000); frequency is unknown - it is impossible to determine based on the available data.
From the circulatory and lymphatic systems
: very rarely - hematopoietic disorders (anemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis), hemolytic anemia. Patients on long-term treatment with NSAIDs should have regular blood tests.
From the immune system:
often - allergic reactions (such as itching or skin rash); infrequently - urticaria; very rarely - allergic vasculitis, pneumonitis, severe allergic reactions. They may manifest themselves as swelling of the face, swelling of the tongue and posterior part of the pharynx with narrowing of the airways, difficulty breathing, tachycardia and a drop in blood pressure, and sometimes anaphylactic shock may develop.
From the nervous system:
often - headache, dizziness, irritability or fatigue; very rarely - sensory disturbances, taste disturbances, memory disturbances, disorientation, convulsions, tremors, psychotic reactions, depression, anxiety, nightmares.
From the side of the organ of vision:
very rarely - blurred vision, diplopia, decreased vision.
Hearing and labyrinth disorders:
often - vertigo; very rarely - “ringing” in the ears, hearing loss.
From the cardiovascular system
: very rarely - hypertension, palpitations, chest pain, myocardial infarction, cardiac arrest.
From the gastrointestinal tract:
very often - gastrointestinal disorders (nausea, vomiting, diarrhea, minor gastrointestinal bleeding, in some cases leading to anemia); often - dyspepsia, flatulence, colic and abdominal pain, loss of appetite, gastrointestinal ulcers (in some cases accompanied by bleeding and perforation); infrequently - gastritis, bloody vomiting, melena, bloody diarrhea; very rarely - stomatitis, glossitis, lesions of the esophagus, dysfunction of the lower gastrointestinal tract (hemorrhagic colitis), exacerbation of ulcerative colitis or Crohn's disease, constipation, pancreatitis.
Liver function
: often - increased levels of “liver” transaminases in the serum; rarely - impaired liver function, especially with long-term treatment, acute hepatitis, accompanied by jaundice or without jaundice (in very rare cases with immediate development without noticeable prodromal symptoms with the development of hepatic coma and liver necrosis).
From the skin
: often - skin rash; very rarely - exanthema, eczema, erythema, hair loss, sensitivity to light, purpura (including allergic), bullous reactions (including Stevens-Johnson syndrome) and toxic epidermal necrolysis, bullous dermatitis, toxic epidermal necrolysis (Lyell's syndrome).
From the kidneys and urinary tract system,
very rarely - renal failure and urinary pathologies (hematuria, proteinuria, interstitial nephritis, nephrotic syndrome and papillary necrosis), decreased urinary volume.
Other:
often - reaction at the injection site; uncommon - edema (especially in patients with arterial hypertension or renal failure); rarely - aseptic necrosis, necrosis of adipose tissue; very rarely - abscess at the injection site. In very rare cases, in patients systematically taking NSAIDs, there was a worsening of inflammatory conditions of infectious origin (the development of necrotizing fasciitis). If during therapy with Diclonate P the patient develops an infectious disease or a relapse of an existing infectious disease, the patient should urgently seek appropriate medical help and, if necessary, undergo treatment with antibacterial drugs.
Very rarely, when treated with Diclonate P, patients were diagnosed with signs of aseptic meningitis, such as a stiff neck, nausea, vomiting, fever or clouding of consciousness. According to available data, patients suffering from autoimmune diseases (systemic lupus erythematosus, mixed connective tissue disease) may be predisposed to similar symptoms.
The results of clinical studies, as well as epidemiological data, suggest that therapy with Diclonate P, especially long-term and in high doses (150 mg/day), may cause a slight increase in the risk of thrombotic events.
damage to arterial vessels (for example, myocardial infarction or stroke).
Cases of peripheral edema, hypertension and heart failure have been reported during NSAID therapy.
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.
Diclofenac 25 mg and 50 mg, tablets
When taking all NSAIDs, gastrointestinal bleeding, ulceration and perforation are possible, which can be fatal and occur during treatment against the background of warning symptoms, or in the absence of them, or in patients with a history of serious gastrointestinal diseases. In general, such phenomena are most dangerous for elderly patients. In some cases, when these complications develop in patients taking Diclofenac, the drug must be discontinued. While taking Diclofenac, medical supervision is necessary for patients with diseases of the gastrointestinal tract or a history of gastric or intestinal ulcers, ulcerative colitis or Crohn's disease.
To reduce the risk of toxic effects on the gastrointestinal tract in patients with a history of peptic ulcer, in particular, complicated by bleeding and perforation, as well as in elderly patients, treatment should be started with the lowest effective dose and maintained thereafter. In the above patients and patients requiring concomitant use of drugs containing low doses of acetylsalicylic acid (ASA)/aspirin or other drugs that may increase the risk of developing adverse reactions from the gastrointestinal tract, the advisability of combination therapy in combination with protective drugs should be considered. medications (for example, proton pump inhibitors or misoprostol).
NSAIDs may increase the risk of serious cardiovascular thrombotic events, myocardial infarction and stroke, which can be fatal, and therefore Diclofenac is not recommended for the treatment of postoperative pain in the case of coronary artery bypass surgery.
Severe, even fatal, skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been very rarely reported with NSAIDs, including Diclofenac. The highest risk of these reactions occurs at the beginning of therapy, and the development of these reactions is observed in most cases in the first month of treatment. Diclofenac should be discontinued at the first manifestation of skin rash, mucosal ulcers or any other manifestations of hypersensitivity. In patients who have not previously taken Diclofenac, during treatment with the drug, as well as during therapy with other NSAIDs, in rare cases, allergic reactions may develop, including anaphylactic and anaphylactoid reactions.
Diclofenac can mask symptoms characteristic of infectious and inflammatory diseases.
Elderly patients should take the drug with caution. In particular, frail elderly patients and patients with low body weight are recommended to take the lowest effective dose.
Diclofenac tablets contain lactose, so their use is not recommended in patients with hereditary galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption.
Patients with asthma, seasonal allergic rhinitis, nasal edema, chronic obstructive pulmonary disease, or chronic respiratory tract infections are more likely to experience allergic reactions to NSAIDs than other patients. Particular care should be taken when treating such patients.
If Diclofenac is prescribed to patients with impaired liver function, medical supervision of their condition is necessary, since an exacerbation of the disorders is possible. During the use of Diclofenac, as well as other NSAIDs, the level of one or more liver enzymes may increase. Therefore, during long-term therapy with Diclofenac, regular liver function testing is indicated as a preventive measure. If abnormalities in liver function parameters persist or worsen, if complaints or symptoms indicating liver disease develop, as well as if other side effects occur (for example, eosinophilia, rash, etc.), the drug should be discontinued. It must be borne in mind that hepatitis when taking the drug can occur without prodromal phenomena. Caution should be exercised when prescribing Diclofenac to patients with hepatic porphyria, as it may provoke an exacerbation.
Because prostaglandins play an important role in maintaining renal blood flow, special caution is required when treating patients with impaired cardiac or renal function.
(including those with functional renal failure due to hypovolemia, nephrotic syndrome, lupus nephropathy and decompensated cirrhosis of the liver), elderly patients, patients with a history of hypertension, patients using diuretics, as well as patients who have a significant decrease volume of circulating plasma of any etiology, for example, during the period before and after major surgical interventions. In these cases, while taking Diclofenac, it is recommended that regular monitoring of renal function is carried out as a precautionary measure. Discontinuation of the drug usually results in restoration of renal function to baseline levels. With long-term use of Diclofenac, like other NSAIDs, systematic monitoring of the condition of peripheral blood is indicated.
Diclofenac, like other NSAIDs, can temporarily inhibit platelet aggregation, so patients with hemostasis disorders require careful monitoring of relevant laboratory parameters.