Diclofenac-Solofarm, 25 mg/ml 3 ml 5 pcs

Pharmacotherapeutic group

A nonsteroidal anti-inflammatory drug (NSAID).

ATX code: M01AB05

Pharmacological properties

Pharmacodynamics<

Diclofenac has anti-inflammatory, analgesic and antipyretic effects. Indiscriminately inhibiting cyclooxygenase 1 and 2, disrupts the metabolism of arachidonic acid, reduces the number of prostaglandins in the focus of inflammation. In rheumatic diseases anti-inflammatory and analgesic effect of diclofenac contributes to a significant reduction in the severity of pain, morning stiffness, joint swelling that improves the functional state of the joint. In trauma, in postoperative period diclofenac reduces pain and inflammatory swelling.

Pharmacokinetics

Absorption

After intramuscular administration of diclofenac its absorption begins immediately. The maximum plasma concentration (Cmax), averaging about 2.5 µg/mL (8 µmol/L), is reached after about 20 minutes. The amount of absorbed active ingredient is linearly related to the dose of the drug. The area under the curve “concentration-time” (AUC) after intramuscular diclofenac administration is approximately 2 times greater than after its oral or rectal administration, because in the latter cases, about half of diclofenac is metabolized during the “first passage” through the liver. Pharmacokinetic parameters do not change during subsequent administration of the drug. No cumulation is noted if the recommended intervals between doses of the drug are observed.

Distribution

The binding to serum proteins is 99.7%, mostly to albumin (99.4%). The apparent 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 blood plasma. The apparent half-life (T½) from synovial fluid is 3-6 hours. Two hours after reaching maximum plasma concentration, the concentration of diclofenac in synovial fluid is higher than in plasma, and its values remain higher for up to 12 hours.

Metabolism

. Diclofenac is metabolized partly by glucuronidation of the unchanged molecule, but mainly by single and multiple hydroxylation and methoxylation, resulting in 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. The two phenolic metabolites are biologically active, but to a much lesser extent than diclofenac. The CYP2C9 isoenzyme is involved in metabolism of the drug.

The total systemic plasma clearance of diclofenac is 263 ± 56 ml/min. The final T½ is 1-2 hours. The T½ of the 4 metabolites, including the two pharmacologically active ones, is similarly short and is 1-3 hours. One of the metabolites, 3′-hydroxy-4′-methoxydiclofenac, has a longer T½, but this metabolite is completely inactive. About 60% of the drug dose is excreted through the kidneys as glucuron conjugates of the unchanged active substance, as well as metabolites, most of which are also glucuron conjugates. Less than 1% of diclofenac is excreted unchanged. The remaining part of the drug dose is excreted as metabolites in the bile.

Pharmacokinetics in individual groups of patients

Pharmacokinetic parameters of diclofenac do not change in elderly patients. In patients with impaired renal function there is no cumulation of unchanged active substance while following the recommended dosing regimen. When creatinine clearance is less than 10 ml/min, calculated equilibrium concentrations of diclofenac hydroxymetabolites are about 4 times higher than in healthy volunteers, and metabolites are excreted only with bile. In patients with chronic hepatitis or compensated liver cirrhosis pharmacokinetic parameters of diclofenac are similar to those of patients without liver disease. Diclofenac penetrates into breast milk.

Indications

For short-term treatment of pain of different genesis, of moderate intensity:

The drug is intended for symptomatic therapy, pain and inflammation decrease at the moment of use, it has no effect on disease progression.

Active ingredient

Composition

Composition of the drug per 1 ml

Active substance:

Diclofenac sodium – 25 mg

Particulate matter:

Mannitol-6 mg

Propylene glycol-200 mg

Benzyl alcohol-40 mg

Sodium disulfite 0.6 mg

Sodium hydroxide solution 1 M- to pH 7.8-8.8

Injection water- up to 1 ml

How to take, the dosage

Interaction

Enhances plasma concentrations of digoxin, methotrexate, lithium drugs and cyclosporine. Reduces the effect of diuretics; against potassium-saving diuretics increases the risk of hyperkalemia; against anticoagulants, thrombolytic agents (alteplase, streptokinase, urokinase) – risk of bleeding (often from the gastrointestinal tract). Reduces the effects of hypotensive and sleeping pills.

Increases the likelihood of side effects of other nonsteroidal anti-inflammatory drugs and glucocorticosteroids (bleeding in the gastrointestinal tract), methotrexate toxicity and cyclosporine nephrotoxicity. Acetylsalicylic acid reduces the blood concentration of diclofenac.

Concomitant use with paracetamol increases the risk of nephrotoxic effects of diclofenac. Reduces the effect of hypoglycemic agents. Cefamandole, cefoperazone, cefotetan, valproic acid and plikamycin increase the incidence of hypoprothrombinemia. Cyclosporine and gold drugs increase the effect of diclofenac on the synthesis of prostaglandins in the kidneys, which increases nephrotoxicity.

Concomitant administration with ethanol, colchicine, corticotropin, selective serotonin reuptake inhibitors and St. John’s wort preparations increases the risk of gastrointestinal bleeding. Diclofenac increases the effect of drugs that cause photosensitization. Drugs that block tubular secretion increase the plasma concentration of diclofenac, thereby increasing its toxicity. Diclofenac has an antiprostaglandin effect, so diclofenac should not be used for 8-12 days after mifepristone.

Special Instructions

To reduce the risk of adverse events, the lowest effective dose of diclofenac should be used for the shortest possible course. Prolonged therapy with diclofenac and therapy with high doses may increase the risk of serious cardiovascular thrombotic complications (including myocardial infarction and stroke).

Influence on driving and operating machinery

Patients with dizziness and other central nervous system disorders should refrain from driving and operating dangerous machinery during treatment.

Synopsis

Contraindications

Hypersensitivity (including to other NSAIDs or auxiliary components). NSAIDs or auxiliary components), gastrointestinal erosive ulcers (acute phase), bleeding from the gastrointestinal tract, inflammatory bowel disease, marked liver failure, liver disease in the acute period, Severe renal insufficiency (creatinine clearance less than 30 ml/min), hyperkalemia, complete or incomplete intolerance of acetylsalicylic acid (rhinosinusitis, urticaria, nasal polyps, bronchial asthma caused by taking acetylsalicylic acid or other NSAIDs), bleeding disorders, hemostasis disorders (including hemophilia).including hemophilia), pregnancy, childhood (under 18 years), lactation, period after coronary artery bypass grafting, at increased risk of arterial thrombosis and thromboembolism, clinically confirmed ischemic heart disease, peripheral arteries and cerebrovascular disease, chronic heart failure, functional class II-IV according to NYHA classification, uncontrolled arterial hypertension.

With caution

Oedema syndrome, peripheral arterial disease, dyslipidemia, diabetes, anemia, bronchial asthma, defects in the hemostatic system, with risk of cardiovascular thrombosis (including myocardial infarctions and strokes), renal insufficiency (creatinine clearance 30-60 ml/min), alcoholism, gastrointestinal erosive-ulcer disease without exacerbation, Helicobacter pylori infection, diverticulitis, conditions after major surgery, inducible porphyria, advanced age, smoking, severe somatic diseases, systemic connective tissue diseases, long-term use of non-steroidal anti-inflammatory drugs.

Persons with seasonal allergic rhinitis, nasal mucosal edema (including nasal polyps), chronic infectious respiratory diseases (especially those associated with allergic rhinitis-like symptoms) should be used with caution. Special caution should be exercised when using diclofenac in patients receiving drugs that increase the risk of gastrointestinal bleeding: systemic glucocorticosteroids (incl. prednisolone), anticoagulants (incl.including warfarin), antiplatelet agents (including acetylsalicylic acid, clopidogrel) or selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline).

Side effects

To estimate the incidence of diclofenac adverse reactions (various dosage forms), the following gradations were used: “very often” >1/10; “often” from >1/100 to <1/10, “infrequently” from >1/1000 to <1/100, “rarely” from >1/10000 to <1/1000, “very rarely” from <1/10000, including individual reports.

Gastrointestinal side: Frequent – epigastric pain, nausea, vomiting, diarrhea, dyspepsia, flatulence, anorexia, increased aminotransferase activity; rare – gastritis, proctitis, gastrointestinal tract (GIT) bleeding (vomiting with blood, melena, diarrhea with blood admixture), GIT ulcers (with or without bleeding or perforation), hepatitis, jaundice, liver function impairment; very rarely – stomatitis, glossitis, esophagitis, nonspecific hemorrhagic colitis, exacerbation of ulcerative colitis or Crohn’s disease, constipation, pancreatitis, fulminant hepatitis, hepatorenal syndrome.

Nervous system disorders: frequently – headache, dizziness; rarely – somnolence; very rarely – sensory disorders (including paraesthesia), memory disorders, tremor, seizures, anxiety, cerebrovascular disorders, aseptic meningitis, disorientation, depression, insomnia, “nightmares” dreams, irritability, mental disorders.

Sensory organs: Often – vertigo; very rarely – visual impairment (blurred vision, diplopia), hearing disorders, tinnitus, impaired sense of taste.

Skin disorders: Often – skin rash; rarely – urticaria; very rarely – bullous rash, erythema, including erythema multiforme and Stevens-Johnson syndrome, Lyell syndrome, exfoliative dermatitis, itching, hair loss, photosensitization, purpura, including allergic.

Urinary system disorders: Very rarely – acute renal failure, hematuria, proteinuria, interstitial nephritis, nephrotic syndrome, papillary necrosis. Blood organs: Very rarely – thrombocytopenia, leukopenia, hemolytic and aplastic anemia, agranulocytosis, eosinophilia.

Respiratory system disorders: Rarely – bronchial asthma (including dyspnea), cough, laryngeal edema; very rarely – pneumonitis.

Cardiovascular system disorders: Very rare – palpitations, chest pain, increased blood pressure, vasculitis, heart failure, myocardial infarction. Allergic manifestations: Rarely – anaphylactic/anaphylactoid reactions, including marked decrease in blood pressure and shock; very rare – angioedema (including face).

Others: Often – irritation at the injection site; very rare – abscess at the injection site; rarely – edema.

Overdose

Symptoms: Vomiting, dizziness, headache, shortness of breath, confusion, in children – myoclonic convulsions, nausea, vomiting, abdominal pain, bleeding, liver and kidney function disorders, respiratory depression, coma.

Treatment: Symptomatic therapy, forced diuresis. Hemodialysis is ineffective.

Pregnancy use

Similarities