Diclofenac

Diclofenac is a drug from the NSAID group. It has a pronounced anti-inflammatory, analgesic and weak antipyretic effect; the principle of its therapeutic effect is expressed in slowing down the processes of PG binding.

In the case of development of various inflammations that appear after injuries or operations, this drug quickly relieves pain that occurs when making movements, as well as spontaneous pain. [ 1 ]

Indications Diclofenac

It is used for the following disorders:

• rheumatic lesions of a degenerative and inflammatory nature (rheumatoid or juvenile rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and spondyloarthritis );
• pain developing in the spine;
• rheumatic diseases affecting extra-articular soft tissues;
• acute gouty attacks;
• pain that develops after surgery or injury, against the background of which swelling and inflammation are observed (for example, after orthopedic or dental procedures);
• gynecological pathologies that cause inflammation and pain (for example, adnexitis or primary dysmenorrhea);
• as an adjuvant medicine for severe inflammatory diseases affecting the ENT organs, accompanied by severe pain (for example, otitis or pharyngotonsillitis).

Release form

The release of the therapeutic substance is realized in tablets - 10 pieces inside a cell plate; inside a box - 1 or 3 such plates.

Pharmacodynamics

The drug inhibits platelet aggregation. It also reduces pain during movement and at rest, joint swelling and stiffness in the morning; it helps improve the functional activity of the joints. [ 2 ]

Pharmacokinetics

Diclofenac Na is absorbed into the blood at high speed, reaching plasma Cmax values after 1-2 hours. Protein synthesis is 99%.

It penetrates well into synovium and tissues, where the drug levels increase slowly; after 4 hours it reaches a level exceeding plasma values. Food may reduce the rate of absorption, but does not change its extent. The bioavailability level is approximately 5%. [ 3 ]

The plasma half-life is 1-2 hours; synovial half-life is 3-6 hours. Approximately 35% of the drug is excreted in the form of metabolic elements with feces; approximately 65% is involved in intrahepatic metabolic processes and is excreted through the kidneys in the form of inactive derivatives; approximately 1% is excreted unchanged.

Dosing and administration

The medicine is taken orally, in minimal effective doses for the shortest period of time - to reduce the risk of side effects. Tablets are taken with or after food, washed down with water and without chewing. The size of the Diclofenac portion and the duration of administration are selected by the doctor, taking into account the course and nature of the disease, the patient's reaction and the drug's effectiveness.

The initial dose is often 0.1-0.15 g per day. For mild symptoms and long-term treatment, a dose of 75-100 mg per day is sufficient. The daily dose should be divided into 2-3 uses.

In the case of the primary form of dysmenorrhea, the daily dosage is selected individually, often it is equal to 0.05-0.15 g. The initial portion can be 50-100 mg, but if necessary, it can be increased over several menstrual cycles to the maximum level of 0.2 g per day. You need to start using the drug after the development of the first painful manifestations and continue for several days, taking into account the dynamics of regression of the signs of the disorder.

The maximum recommended daily dose of the medication is 0.15 g.

• Application for children

Tablets should not be used before the age of 14. Teenagers aged 14-18 are prescribed the medicine in a dose of 75-150 mg per day, in 2-3 doses.

Use Diclofenac during pregnancy

Diclofenac should not be used during pregnancy. If the drug needs to be used during breastfeeding, the issue of stopping breastfeeding should be resolved.

The drug has a negative effect on a woman's fertility, which is why it is not prescribed when planning a pregnancy. Women who have problems with conception or undergo infertility tests should consider discontinuing the drug.

Contraindications

Main contraindications:

• severe intolerance to the active ingredient or other components of the drug;
• active form of ulcer in the gastrointestinal tract;
• perforation or bleeding in the gastrointestinal area;
• history of perforation or bleeding in the gastrointestinal tract caused by the use of NSAIDs;
• history of acute or recurrent bleeding/ulcer (2+ separate diagnosed episodes of bleeding or ulceration);
• inflammation in the intestinal area (for example, ulcerative colitis or regional enteritis);
• renal/liver failure;
• severe or congestive form of heart failure;
• IHD in people with a history of myocardial infarction or angina pectoris;
• cerebrovascular lesions in individuals who have suffered a stroke or had episodes of TIA;
• diseases affecting peripheral arteries;
• for the treatment of postoperative pain during coronary artery bypass grafting (or in the case of the use of artificial cardiac output);
• in the development of reactions such as urticaria, asthma attacks, nasal polyps, active rhinitis, Quincke's edema and other signs of allergy in response to the use of NSAIDs;
• blood disorders.

Side effects Diclofenac

Side effects include:

• disorders of the lymphatic and hematopoietic system: leukopenia or thrombocytopenia, agranulocytosis, anemia (also aplastic or hemolytic);
• immune disorders: increased temperature, Quincke's edema (also swelling of the face), hypersensitivity, anaphylactoid and anaphylactic symptoms (including shock and decreased blood pressure);
• mental problems: insomnia, disorientation, nightmares, irritability, depression and psychotic disorders;
• Symptoms related to the function of the nervous system: drowsiness, convulsions, paresthesia, headache and fatigue, as well as dizziness, taste disturbances, memory problems and tremor. In addition, aseptic meningitis, asthenia, anxiety, stroke and confusion, cerebral blood flow disorder, sensory disturbance and hallucinations;
• visual disturbances: vision problems, diplopia, blurred vision and neuritis affecting the optic nerve;
• labyrinth and hearing disorders: tinnitus, vertigo and auditory disturbances;
• problems in the cardiovascular system: palpitations, increased respiratory rate, asthenia, heart failure, dyspnea, increased pulse rate, increased/decreased blood pressure, myocardial infarction, chest pain and vasculitis;
• lesions affecting the organs of the sternum, respiratory system and mediastinum: pneumonitis and asthma (including dyspnea);
• digestive disorders: diarrhea, nausea, loss of appetite and flatulence, vomiting, heartburn, dyspepsia, abdominal pain and taste disturbance. In addition, gastritis, constipation, glossitis, anorexia, bleeding in the gastrointestinal tract (melena, vomiting and diarrhea with blood), colitis (also hemorrhagic form, regional enteritis and exacerbation of ulcerative colitis), ulcers in the gastrointestinal tract, which may lead to perforation or bleeding (sometimes fatal, especially in the elderly). Stomatitis (including its ulcerative form), pancreatitis, gastric erosion, esophageal dysfunction, diaphragmatic intestinal stenosis and gastroenteropathy, accompanied by polyserositis, malabsorption and maldigestion also develop;
• hepatobiliary dysfunction: hepatitis (also fulminant form), liver failure and increased transaminase levels, liver dysfunction, jaundice and liver necrosis;
• lesions of the subcutaneous layer and epidermis: hyperemia, SJS, rashes (papular, punctate or maculo-urticarial), erythema multiforme, TEN, urticaria, alopecia, rashes in the form of blisters, purpura (also of an allergic nature), eczema, exfoliative dermatitis, itching and signs of photosensitivity;
• problems with urinary and renal function: hematuria, nephrotic syndrome, acute renal failure, renal papillary necrosis, proteinuria and tubulointerstitial nephritis;
• systemic disorders: edema;
• Disorders related to the reproductive system: impotence.

Clinical trials and epidemiological data show that diclofenac, especially in large doses (0.15 g per day) and in case of long-term use, may increase the risk of developing arterial thromboembolism (for example, stroke or myocardial infarction).

Overdose

Poisoning may cause epigastric pain, diarrhea, nausea, gastrointestinal bleeding, vomiting, disorientation, headache, agitation, drowsiness, dizziness, convulsions, tinnitus, or coma. Severe overdose may cause liver damage and acute renal failure.

Symptomatic and supportive treatments are used to treat acute NSAID intoxication. For example, in cases of renal failure, respiratory depression, decreased blood pressure, seizures, and gastrointestinal dysfunction. Activated carbon may be used when potentially toxic doses are taken, and if a life-threatening dose has been taken, vomiting should be induced and gastric lavage performed.

Interactions with other drugs

The use of the drug together with lithium or digoxin increases the plasma level of the latter, which is why it is necessary to monitor serum lithium and digoxin levels.

Antihypertensive and diuretic drugs.

Administration of the drug together with ACE inhibitors or β-blockers may reduce their hypotensive activity due to slowing down of binding of vasodilatory PGs. In this regard, such a combination should be used with caution, especially in elderly people who need to closely monitor blood pressure values. Patients need appropriate hydration and monitoring of renal function (especially with regard to ACE inhibitors and diuretics, since the likelihood of nephrotoxicity increases).

Medicines that can cause hyperkalemia.

Combination with cyclosporine, trimethoprim, potassium-sparing diuretics or tacrolimus may result in an increase in serum potassium. Therefore, the patient's condition should be monitored regularly.

Antithrombotic drugs and anticoagulants.

Use with Diclofenac may increase the risk of bleeding, so caution is required. Large doses of the drug may temporarily inhibit platelet aggregation.

Other NSAIDs, including corticosteroids and selective COX-2 inhibitors.

With such combinations, the likelihood of developing an ulcer or bleeding in the gastrointestinal tract increases, so you should avoid the combined use of 2+ NSAIDs.

Drugs from the SSRI group.

Such combinations increase the likelihood of developing bleeding in the gastrointestinal tract.

Methotrexate.

The drug can inhibit the clearance of methotrexate inside the renal tubules, which is why the latter's indicators increase. Diclofenac should be used with caution at least 24 hours before the administration of methotrexate, since this may increase the blood level of methotrexate and potentiate its toxic activity.

Cyclosporine.

The drug's effect on intrarenal PG binding may potentiate the nephrotoxic properties of cyclosporine, which is why diclofenac should be administered in reduced doses compared to individuals not using cyclosporine.

Tacrolimus.

The combination of tacrolimus and NSAIDs increases the likelihood of nephrotoxicity, which may be mediated by intrarenal antiprostaglandin reactions of the NSAID and the calcineurin inhibitor.

Antibacterial quinolones.

Convulsions may occur with this combination (possibly in people with or without a history of seizures or epilepsy). This should be taken into account when deciding on the use of quinolones in people already taking NSAIDs.

Phenytoin.

The use of the drug together with phenytoin requires constant monitoring of the plasma values of the latter, since its effect may be enhanced.

Cholestyramine and cholestipol.

These drugs can weaken or delay the absorption of diclofenac, so it is prescribed at least 1 hour before or 4-6 hours after using cholestyramine/colestipol.

SG.

The administration of diclofenac with SG may potentiate cardiac failure, increase plasma glycoside levels and decrease SCF values.

Mifepristone.

NSAIDs should not be used within 8-12 days of mifepristone administration, as they weaken its therapeutic activity.

Substances that inhibit the action of CYP2C9.

When using the drug together with such agents (for example, voriconazole), a significant increase in the exposure and plasma Cmax values of Diclofenac is possible due to the suppression of the metabolic processes of the latter.

Storage conditions

Diclofenac should be stored in a place out of reach of small children. Temperature indicators – no more than 25ºС.

Shelf life

Diclofenac can be used for a period of 36 months from the date of manufacture of the medicinal product.

Analogues

The drug's analogues are Voltaren, Naklofen and Ortofen with Diclofarm, as well as Diclovit and Dialrapid.