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

Indications Diclofenac

It is used for such violations:

• 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 which swelling and inflammation are noted (for example, after orthopedic or dental procedures);
• gynecological pathologies in which inflammation and pain occur (for example, adnexitis or dysmenorrhea of a primary nature);
• as an auxiliary medicine for severe inflammatory diseases affecting the ENT organs, accompanied by severe pain (for example, otitis media or pharyngotonsillitis).

Release form

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

Pharmacodynamics

The drug inhibits platelet aggregation. Also reduces pain during movement and rest, joint swelling and stiffness in the morning; helps to 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 the synovium and tissues, where the drug indicators rise slowly; after 4 hours, it reaches a level that exceeds plasma values. Food can reduce the rate of absorption, but does not alter the rate. The bioavailability level is approximately 5%. [3]

The term plasma half-life is 1–2 hours; synovial half-life - 3-6 hours. Approximately 35% of drugs are excreted in the form of metabolic elements with feces; about 65% - participates in intrahepatic metabolic processes and is excreted through the kidneys in the form of non-active derivatives; approximately 1% is displayed unchanged.

Dosing and administration

The medicine is taken orally, in the minimum effective dosages for the shortest period of time - to reduce the risk of side symptoms. The tablets are taken with food or after it, washed down with water and not chewing. The size of the serving of Diclofenac and the duration of admission are selected by the doctor, taking into account the course and nature of the disease, the patient's response and drug efficacy.

The starting portion is often 0.1-0.15 g per day. With mild manifestations of the disorder and prolonged treatment, a dosage of 75-100 mg per day is sufficient. The daily portion should be divided into 2-3 uses.

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

The size of the maximum recommended portion of the medication per day is 0.15 g.

• Application for children

The tablets should not be used until the age of 14. For adolescents 14-18 years old, the medicine is prescribed in portions of 75-150 mg per day, in 2-3 uses.

Use Diclofenac during pregnancy

Diclofenac should not be used during pregnancy. If the medicine needs to be used for HB, the issue of canceling feeding should be resolved.

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

Contraindications

The main contraindications:

• severe intolerance to the active element or other components of the drug;
• active form of ulcers in the gastrointestinal tract;
• perforation or bleeding in the gastrointestinal area;
• a 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 ulcer);
• inflammation in the intestinal region (for example, ulcerative colitis or regional enteritis);
• failure of kidney / liver function;
• severe or stagnant form of heart failure;
• IHD in people with myocardial infarction or angina pectoris;
• cerebrovascular lesions in persons who have had a stroke or have had episodes of TIA;
• diseases affecting peripheral arteries;
• for the treatment of postoperative pain in coronary artery bypass grafting (or in the case of using AIC);
• with the development in response to the use of NSAIDs of reactions such as urticaria, asthma attacks, nasal polyps, an active form of the common cold, Quincke's edema and other signs of allergy;
• disorders of hematopoiesis.

Side effects Diclofenac

Among the side effects:

• disorders of lymph function and hematopoietic system: leuko- or thrombocytopenia, agranulocytosis, anemia (also aplastic or hemolytic);
• immune disorders: an increase in temperature, Quincke's edema (also facial swelling), hypersensitivity, anaphylactoid and anaphylactic symptoms (including shock and a decrease in blood pressure);
• mental problems: insomnia, disorientation, nightmares, irritability, depression and psychotic disorders;
• symptoms associated with NS function: drowsiness, seizures, paresthesia, cephalalgia and fatigue, as well as dizziness, taste disturbances, memory problems and tremors. In addition, the aseptic form of meningitis, asthenia, anxiety, stroke and confusion, disturbance of intracerebral blood flow, impaired sensitivity and hallucinations;
• visual disturbances: vision problems, diplopia, blurred vision, and neuritis affecting the optic nerve;
• disorders in the labyrinth and hearing: ear ringing, vertigo and hearing disorders;
• problems in the field of CVS: palpitations, increased respiratory rate, asthenia, heart failure, dyspnea, increased heart rate, increase / decrease in blood pressure, myocardial infarction, chest pain and vasculitis;
• lesions affecting the organs of the sternum, respiratory system and mediastinum: pneumonitis and asthma (including dyspnea);
• disorders of the digestive function: 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 bloody diarrhea), colitis (also hemorrhagic form, regional enteritis and exacerbation of ulcerative colitis), ulcers in the gastrointestinal tract, in which perforation may occur or bleeding (sometimes fatal, especially in the elderly). Stomatitis (including its ulcerative form), pancreatitis, gastric erosion, esophageal dysfunction, intestinal stenosis of the diaphragmatic type and gastroenteropathy, accompanied by polyserositis, malabsorption and maldigestion, also develop;
• violations of hepatobiliary function: hepatitis (also fulminant form), liver failure and an increase in transaminase values, hepatic disorders, jaundice and hepatic necrosis;
• lesions of the subcutaneous layer and epidermis: hyperemia, SS, rashes (papular, pinpoint or macular urticaria), erythema polyformis, TEN, urticaria, alopecia, blister-shaped rashes, purpura (also allergic), eczema, exfoliative, pruritic and dermatitis signs of photosensitivity;
• problems with urinary and renal activity: hematuria, nephrotic syndrome, acute renal failure, renal papillary necrosis, proteinuria and tubulointerstitial nephritis;
• systemic disorders: swelling;
• reproductive system disorders: impotence.

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

Overdose

In case of poisoning, epigastric pain, diarrhea, nausea, bleeding in the gastrointestinal tract, vomiting, disorientation, cephalalgia, agitation, drowsiness, dizziness, convulsions, ear noise, or coma may occur. In severe overdose, hepatic damage and acute renal failure may develop.

For the treatment of acute intoxication with NSAIDs, symptomatic and supportive procedures are performed. For example, in case of failure of the kidneys, suppression of breathing, a decrease in blood pressure, seizures and disorders of the gastrointestinal tract. When using potentially toxic dosages, activated charcoal can be used, and if a life-threatening dose has been taken, it is necessary to induce vomiting and perform gastric lavage.

Interactions with other drugs

The use of the drug together with lithium or digoxin increases the plasma index of the latter, which is why it is necessary to control the serum values of lithium and digoxin.

Antihypertensive and diuretic drugs.

The introduction of a drug together with an ACE inhibitor or β-blockers can reduce their hypotensive activity due to a slowdown in the binding of vasodilating PGs. In this regard, this combination should be used with caution, especially in the elderly, who need to carefully monitor blood pressure values. Patients need adequate hydration and control of kidney function (especially with regard to ACE inhibitors and diuretics, since the likelihood of nephrotoxicity increases).

Medicines that can provoke hyperkalemia.

Taking in combination with cyclosporine, trimethoprim, potassium-sparing diuretics, or tacrolimus can lead to an increase in serum potassium. Because of this, you need to regularly monitor the patient's condition.

Antithrombotic drugs and anticoagulants.

Using with Diclofenac may increase the chance of bleeding, so caution must be exercised. Large doses of the drug can temporarily suppress platelet aggregation.

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

With such combinations, the likelihood of developing an ulcer or bleeding in the gastrointestinal tract increases, so you need to abandon the joint use of 2+ NSAIDs.

Preparations from the SSRI group.

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

Methotrexate.

The medication is able to inhibit the clearance of methotrexate inside the renal tubules, due to which the indicators of the latter increase. It is necessary to carefully apply diclofen at least 24 hours before the introduction of methotrexate, since this may increase the blood level of methotrexate and potentiate its toxic activity.

Cyclosporine.

The effect of the drug on the binding of GHGs inside the kidneys can potentiate the nephrotoxic properties of cyclosporin, which is why diclofenac must be administered in reduced dosages compared to persons who do not use cyclosporin.

Tacrolimus.

The combination of tacrolimus and NSAIDs increases the likelihood of nephrotoxicity, which may be mediated by intrarenal antiprostaglandin reactions of NSAIDs and a substance that slows down the action of calcineurin.

Antibacterial quinolones.

With this combination, seizures may appear (possibly in people with or without seizures or a history of epilepsy). This must be taken into account when deciding whether to use quinolones in people who are already using NSAIDs.

Phenytoin.

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

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 / cholestipol.

SG.

The introduction of diclofenac with SG can potentiate cardiac insufficiency, increase the plasma glycoside index and decrease the GFR values.

Mifepristone.

NSAIDs cannot be used within 8-12 days from the moment of administration of mifepristone, since they weaken its therapeutic activity.

Substances that slow down the action of CYP2C9.

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

Storage conditions

Diclofenac must be kept out of the reach of small children. Temperature indicators - no more than 25 ° C.

Shelf life

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

Analogs

The analogs of the drug are the medicines Voltaren, Naklofen and Ortofen with Diclofarm, as well as Diklovit and Dialrapid.