Description of the drug DICLOFENAC for systemic use

Description of the drug DICLOFENAC 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 Renewal

Suction

The systemic bioavailability of diclofenac averages 82%. After taking the drug, the maximum concentration of diclofenac in plasma is achieved on average after 4 hours; its average value is 0.5 µg/ml (1.6 µmol/l). Food intake does not have a clinically significant effect on the absorption of the active substance and its systemic bioavailability. During 24 hours of observation after taking the drug, the concentration of diclofenac in plasma averages 13 ng/ml (40 nmol/l). The amount of absorbed active substance is directly dependent on the dose of the drug. Since about half of the amount of diclofenac is metabolized during the “first pass” through the liver, the AUC after taking the drug orally is approximately 2 times less than in the case of parenteral administration of an equivalent dose of diclofenac.

After repeated doses of diclofenac, pharmacokinetic parameters do not change. Provided the recommended dosage regimen for diclofenac is followed, no accumulation is observed. The basal concentration of diclofenac, determined in the morning before taking the next dose, is about 22 ng/ml (70 nmol/l) during treatment with diclofenac, at a dose of 100 mg 1 time per day.

Distribution

Communication with blood plasma proteins is 99.7%, mainly with albumin (99.4%). The volume of distribution is 0.12-0.17 l/kg.

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

Diclofenac was found in low concentrations (100 ng/ml) in the breast milk of one nursing mother. The estimated amount of diclofenac entering the child's body through breast milk is equivalent to 0.03 mg/kg/day.

Biotransformation/Metabolism

The metabolism of diclofenac is carried out partly by glucuronidation of the unchanged molecule, but mainly through single and multiple hydroxylation and 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 phenolic metabolites are biologically active, but to a much lesser extent than diclofenac.

Removal

The total systemic plasma clearance of diclofenac is 263 ± 56 ml/min. The terminal half-life is 1-2 hours. The half-life of 4 metabolites, including two pharmacologically active ones, is also short and amounts to 1-3 hours. One of the metabolites, 3′-hydroxy-4′-methoxy-diclofenac, has a longer half-life, but this metabolite is completely inactive.

About 60% of the dose of diclofenac 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 also glucuronic conjugates. Less than 1% of diclofenac is excreted unchanged. The remainder of the dose of diclofenac is excreted in the form of metabolites in bile.

The concentration of the active substance in the blood plasma depends linearly on the dose taken.

Pharmacokinetics in selected patient groups

Absorption, metabolism and excretion of diclofenac do not depend on age. In patients with impaired renal function, if the recommended dosage regimen is followed, accumulation of unchanged active substance is not observed. When creatinine clearance is less than 10 ml/min, the calculated equilibrium concentrations of diclofenac hydroxymetabolites are approximately 4 times higher than in healthy volunteers, while the metabolites are excreted exclusively in bile.

In patients with chronic hepatitis or compensated liver cirrhosis, the pharmacokinetics of diclofenac are similar to those in patients with preserved liver function.

Diclofenac, 75 mg/3 ml, solution for intramuscular administration, 3 ml, 5 pcs.

Damage to the gastrointestinal tract

When using diclofenac, phenomena such as bleeding or ulceration/perforation of the gastrointestinal tract, in some cases fatal, 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 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 gastrointestinal toxicity in patients with gastrointestinal ulcers, especially complicated by a history of 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 bronchial 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 respiratory tract infections (especially those associated with allergic 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, in patients who are not allergic to diclofenac, anaphylactic/anaphylactoid reactions may develop when using Diclofenac.

Effects on the liver

Since during the period of use of the drug Diclofenac there may be an increase in the activity of one or more liver enzymes, during long-term therapy with the drug, monitoring of liver function is indicated as a precautionary measure. If liver dysfunction persists and progresses or signs of liver disease or other symptoms (for example, eosinophilia, rash, etc.) occur, the drug should be discontinued. It should be borne in mind that hepatitis during the use of the drug 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 circulating blood plasma volume 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.

Impact on the cardiovascular system

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 diseases of the cardiovascular system and a high risk of developing diseases of the cardiovascular system (for example, with arterial hypertension, hyperlipidemia, diabetes mellitus, smokers), the drug should be used with extreme caution, at the lowest effective dose for the shortest 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 the drug 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 the ability to perform potentially hazardous activities that require special attention and quick reactions (driving vehicles, working with moving mechanisms, etc.)

Patients who experience visual disturbances, dizziness, drowsiness, vertigo or other central nervous system disorders while taking diclofenac should not drive or operate machinery.

Diclofenac Retard tablets PPO Prolong 100 mg No. 20

Compound

Active substance: diclofenac sodium - 100 mg. Excipients: lactose monohydrate, corn starch, povidone K-30, sodium lauryl sulfate, sodium carboxymethyl starch, colloidal silicon dioxide, magnesium stearate; shell: methacrylic acid and ethyl acrylate copolymer, macrogol 6000, talc, titanium dioxide E 171 CI 77891, sunset yellow dye [E110].

Pharmacokinetics

After oral administration, it is absorbed from the gastrointestinal tract. Eating slows down the rate of absorption, but the degree of absorption does not change. About 50% of the active substance is metabolized during the “first pass” through the liver. When administered rectally, absorption occurs more slowly. The time to reach Cmax in plasma after oral administration is 2-4 hours depending on the dosage form used, after rectal administration - 1 hour, intramuscular administration - 20 minutes. The concentration of the active substance in plasma is linearly dependent on the dose applied.

Does not accumulate. Plasma protein binding is 99.7% (mainly with albumin). Penetrates into synovial fluid, Cmax is reached 2-4 hours later than in plasma.

It is extensively metabolized to form several metabolites, of which two are pharmacologically active, but to a lesser extent than diclofenac.

Systemic clearance of the active substance is approximately 263 ml/min. T1/2 from plasma is 1-2 hours, from synovial fluid - 3-6 hours. Approximately 60% of the dose is excreted in the form of metabolites by the kidneys, less than 1% is excreted unchanged in the urine, the rest is excreted in the form of metabolites in bile.

Indications for use

Inflammatory and degenerative diseases of the musculoskeletal system, incl. rheumatoid, juvenile, chronic arthritis; ankylosing spondylitis and other spondyloarthropathy; osteoarthritis; gouty arthritis; bursitis, tendovaginitis; pain syndrome from the spine (lumbago, sciatica, ossalgia, neuralgia, myalgia, arthralgia, radiculitis); post-traumatic postoperative pain syndrome accompanied by inflammation (for example, in dentistry and orthopedics); algodismenorrhea; inflammatory processes in the pelvis (including adnexitis); infectious and inflammatory diseases of the ENT organs with severe pain syndrome (as part of complex therapy): pharyngitis, tonsillitis, otitis media.

Isolated fever is not an indication for the use of the drug.

The drug is intended for symptomatic therapy, reducing pain and inflammation at the time of use, and does not affect the progression of the disease.

Contraindications

• Hypersensitivity to diclofenac and any other components of the drug.
• Complete or incomplete combination of bronchial asthma, recurrent nasal polyposis and paranasal sinuses and intolerance to acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (including a history).
• Erosive and ulcerative changes in the mucous membrane of the stomach or duodenum, active gastrointestinal bleeding.
• Inflammatory bowel diseases (ulcerative colitis, Crohn's disease) in the acute phase.

• The period after coronary artery bypass surgery.
• III trimester of pregnancy, breastfeeding period.
• Confirmed chronic heart failure (II-IV functional class according to the NYHA classification).
• Clinically confirmed coronary heart disease.
• Peripheral arterial disease or cerebrovascular disorders.
• Increased risk of arterial thrombosis and thromboembolism.
• Uncontrolled arterial hypertension.
• Hematopoietic disorders, hemostasis disorders (including hemophilia).
• Severe liver failure or active liver disease.
• Severe renal failure (creatinine clearance less than 30 ml/min); progressive kidney diseases.
• Confirmed hyperkalemia.
• Lactose intolerance, lactase deficiency, glucose-galactose malabsorption (the drug contains lactose).
• Children's age up to 14 years.

With caution:
Anemia, bronchial asthma, confirmed chronic heart failure of functional class I according to the NYHA classification, arterial hypertension, edema syndrome, liver or kidney failure (creatinine clearance 30-60 ml/min), dyslipidemia, hyperlipoproteinemia. diabetes mellitus, smoking, inflammatory bowel diseases, condition after major surgical interventions, inducible porphyria, diverticulitis, systemic connective tissue diseases, pregnancy I-II trimester.

Anamnestic data on the development of peptic ulcer disease of the gastrointestinal tract, the presence of Helicobacter pylori infection, old age, long-term use of NSAIDs. frequent alcohol consumption, severe somatic illnesses.

Concomitant therapy with anticoagulants (for example, warfarin), antiplatelet agents (for example, acetylsalicylic acid, clopidogrel), oral glucocorticosteroids (for example, prednisolone), selective serotonin reuptake inhibitors (for example, citalopram, fluoxetine, paroxetine, sertraline).

In patients with 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), with allergies to other drugs, in patients With a significant decrease in circulating blood volume, diclofenac should be used with caution.

Directions for use and doses

The dose of the drug is selected individually, and in order to reduce the risk of side effects, it is recommended to use the minimum effective dose, if possible, with the shortest possible treatment period in accordance with the purpose of treatment and the patient’s condition.

The tablets should be swallowed whole with liquid, preferably before meals. Do not split or chew the tablets.

Adults and teenagers from 14 years old. The recommended dose is 100-150 mg/day. The daily dose should be divided into several doses. To relieve night pain or morning stiffness, in addition to taking the drug during the day, use diclofenac in the form of rectal suppositories before bedtime; in this case, the total daily dose should not exceed 150 mg.

For 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.

For the treatment of rheumatoid arthritis, the daily dose can be increased to a maximum of 3 mg/kg (in several doses). The maximum daily dose should not exceed 150 mg.

Elderly patients (≥ 65 years)

Initial dose adjustment is generally not required in patients aged 65 years and older. However, based on general medical considerations, caution should be exercised in frail elderly patients or patients with low body weight.

Patients with cardiovascular diseases or high risk of cardiovascular diseases

The drug should be used with extreme caution in patients with diseases of the cardiovascular system or a high risk of developing diseases of the cardiovascular system. 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.

Patients with impaired renal function There is no data on the need for dose adjustment when using the drug in patients with impaired renal function due to the lack of safety studies of the drug in patients in this category. Caution should be exercised when using the drug in patients with impaired renal function.

The use of the drug in patients with renal failure (creatinine clearance less than 30 ml/min) is contraindicated (see section "Contraindications").

Patients with impaired liver function. There is no data on the need for dose adjustment when using the drug in patients with mild to moderate liver dysfunction due to the lack of safety studies of the drug in this category of patients.

The use of the drug in patients with severe liver dysfunction is contraindicated (see section “Contraindications”).

Storage conditions

At a temperature not exceeding 25°C in consumer packaging (cardboard pack).

Keep out of the reach of children.

Best before date

3 years. Do not use after the expiration date stated on the package.

special instructions

Use with extreme caution in patients with a history of liver, kidney, gastrointestinal diseases, dyspeptic symptoms, bronchial asthma, arterial hypertension, heart failure, immediately after major surgical interventions, as well as in elderly patients.

If there is a history of allergic reactions to NSAIDs and sulfites, diclofenac is used only in emergency cases. During treatment, systematic monitoring of liver and kidney function and peripheral blood patterns is necessary.

Rectal use is not recommended in patients with diseases of the anorectal region or a history of anorectal bleeding. It should be used externally only on undamaged areas of the skin.

Avoid contact of diclofenac with the eyes (except for eye drops) or mucous membranes. Patients using contact lenses should use eye drops no earlier than 5 minutes after removing the lenses.

Not recommended for use in children under 6 years of age.

During treatment with dosage forms for systemic use, alcohol consumption is not recommended.

Description

NSAIDs.

Pharmacodynamics

NSAID, phenylacetic acid derivative. It has a pronounced anti-inflammatory, analgesic and moderate antipyretic effect. The mechanism of action is associated with inhibition of the activity of COX, the main enzyme in the metabolism of arachidonic acid, which is a precursor of prostaglandins, which play an important role in the pathogenesis of inflammation, pain and fever. The analgesic effect is due to two mechanisms: peripheral (indirectly, through suppression of prostaglandin synthesis) and central (due to inhibition of prostaglandin synthesis in the central and peripheral nervous system).

In vitro, at concentrations equivalent to those achieved when treating patients, it does not inhibit the biosynthesis of cartilage tissue proteoglycans.

For rheumatic diseases, it reduces pain in the joints at rest and during movement, as well as morning stiffness and swelling of the joints, and helps to increase range of motion. Reduces post-traumatic and postoperative pain, as well as inflammatory swelling.

In case of post-traumatic and postoperative inflammatory phenomena, it quickly relieves pain (arising both at rest and during movement), reduces inflammatory swelling and swelling of the postoperative wound.

Suppresses platelet aggregation. With long-term use it has a desensitizing effect.

Side effects

Determination of the frequency of adverse reactions: very often (≥1/10), often (≥1/100, <1/10) infrequently (≥1/1000, <1/100), rarely (≥1/10,000, <1/ 1000), very rare (<1/10,000).

From the digestive system: often - abdominal pain, nausea, vomiting, diarrhea, dyspepsia, flatulence, loss of appetite, anorexia, increased activity of aminotransferases in the blood serum; rarely - gastritis, gastrointestinal bleeding, vomiting blood, melena, diarrhea mixed with blood, stomach and intestinal ulcers (with or without bleeding or perforation), hepatitis, jaundice, liver dysfunction; very rarely - stomatitis, glossitis, damage to the esophagus, the occurrence of diaphragm-like strictures in the intestine, colitis (nonspecific hemorrhagic colitis, exacerbation of ulcerative colitis or Crohn's disease), constipation, pancreatitis, fulminant hepatitis, liver necrosis, liver failure.

From the nervous system: often - headache, dizziness; rarely - drowsiness; very rarely - sensory disturbances, including paresthesia, memory disorders, tremors, convulsions, anxiety, acute cerebrovascular accidents, aseptic meningitis; very rarely - disorientation, depression, insomnia, nightmares, irritability, mental disorders.

From the senses: often - vertigo; very rarely - visual impairment (blurred vision), diplopia, hearing impairment, tinnitus, dysgeusia.

Dermatological reactions: often - skin rash; rarely - urticaria; very rarely - bullous rashes, eczema, erythema, erythema multiforme, Stevens-Johnson syndrome, Lyell's syndrome (toxic epidermal necrolysis), exfoliative dermatitis, itching, hair loss, photosensitivity reactions; purpura, Henoch-Schönlein purpura.

From the genitourinary system: very rarely - acute renal failure, hematuria, proteinuria, tubulointerstitial nephritis, nephrotic syndrome, papillary necrosis.

From the hematopoietic system: very rarely - thrombocytopenia, leukopenia, hemolytic anemia, aplastic anemia, agranulocytosis.

Allergic reactions: rarely - hypersensitivity, anaphylactic/anaphylactoid reactions, including decreased blood pressure and shock; very rarely - angioedema (including facial swelling).

From the cardiovascular system: very rarely - palpitations, chest pain, increased blood pressure, vasculitis, heart failure, myocardial infarction. There is evidence of a slight increase in the risk of developing cardiovascular thrombotic complications (for example, myocardial infarction), especially with long-term use of diclofenac in high doses (daily dose more than 150 mg).

From the respiratory system: rarely - asthma (including shortness of breath); very rarely - pneumonitis.

General reactions: rarely - swelling.

Use during pregnancy and breastfeeding

There is insufficient data on the safety of diclofenac in pregnant women. Therefore, administration in the first and second trimesters of pregnancy is possible only in cases where the expected benefit to the mother outweighs the potential risk to the fetus. Diclofenac (like other inhibitors of prostaglandin synthesis) is contraindicated in the third trimester of pregnancy (possible suppression of uterine contractility and premature closure of the ductus arteriosus in the fetus).

Despite the fact that diclofenac is excreted in breast milk in small quantities, use during lactation (breastfeeding) is not recommended. If use is necessary during lactation, breastfeeding should be discontinued.

Since diclofenac (like other NSAIDs) may have a negative effect on fertility, use in women planning pregnancy is not recommended.

For patients undergoing examination and treatment for infertility, the drug should be discontinued.

Interaction

• Potent CYP2C9 inhibitors: When diclofenac is co-administered with strong CYP2C9 inhibitors (such as voriconazole), diclofenac serum concentrations may increase and systemic effects may increase due to inhibition of diclofenac metabolism.
• Lithium, digoxin - an increase in the concentration of lithium and digoxin in plasma is possible. It is recommended to monitor the concentration of lithium and digoxin in the blood serum.
• Diuretics and antihypertensive drugs - when used simultaneously with diuretics and antihypertensive drugs (for example, beta-blockers, ACE inhibitors), diclofenac may reduce their hypotensive effect.
• Cyclosporine - the effect of diclofenac on the activity of prostate glandins in the kidneys may enhance the nephrotoxicity of cyclosporine.
• Drugs that can cause hyperkalemia - Concomitant use of diclofenac with potassium-sparing diuretics, cyclosporine, tacrolimus and trimethoprim can lead to an increase in plasma potassium levels (in the case of such a combination, this indicator should be monitored frequently).
• Antibacterial agents quinolone derivatives - there are isolated reports of the development of seizures in patients receiving quinolone derivatives and diclofecac simultaneously.
• NSAIDs and GCS - with simultaneous systemic use of diclofenac and other systemic NSAIDs or GCS may increase the incidence of adverse events (in particular, from the gastrointestinal tract).
• Anticoagulants and antiplatelet agents - an increased risk of bleeding cannot be excluded when diclofenac is used simultaneously with drugs from these groups.
• Selective serotonin reuptake inhibitors may increase the risk of gastrointestinal bleeding.
• Hypoglycemic drugs - cases of both hypoglycemia and hyperglycemia cannot be excluded, which necessitated the need to change the dose of hypoglycemic drugs during the use of diclofenac.
• Methotrexate - when diclofenac is used within 24 hours before or within 24 hours after taking methotrexate, the concentration of methotrexate in the blood may increase and its toxic effect may increase.
• Phenytoin - the effect of phenytoin may be enhanced.

Overdose

Symptoms: nausea, vomiting, epigastric pain, bleeding from the gastrointestinal tract. diarrhea, dizziness, headache, tinnitus, convulsions, decreased blood pressure. respiratory depression, with significant overdose - acute renal failure, hepatotoxic effect.

Treatment: gastric lavage, activated charcoal, symptomatic therapy aimed at eliminating arterial hypotension, renal dysfunction, convulsions, gastrointestinal damage, respiratory depression. Forced diuresis and hemodialysis are ineffective (due to the significant connection with proteins and intensive metabolism).

Impact on the ability to drive vehicles and operate machinery

Patients who experience visual disturbances, dizziness, drowsiness or other disorders of the central nervous system while using diclofenac should not drive vehicles or operate machinery.