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

Composition

Composition of the drug per 1 ml

Active ingredient:

Diclofenac sodium– 25 mg

Auxiliary substances:

Mannitol– 6 mg

Propylene Glycol-200 mg

Benzyl alcohol-40 mg

Sodium disulfite-0.6 mg

Sodium hydroxide solution 1 M-up to pH 7.8-8.8

Water for injection-up to 1 ml

Pharmacological action

Pharmacotherapy group

Nonsteroidal anti-inflammatory drug (NSAID).

ATX code: M 01 AB 05

Pharmacological properties

Pharmacodynamics

Diclofenac has anti-inflammatory, analgesic and antipyretic effects. Indiscriminately inhibiting cyclooxygenase 1 and 2, it disrupts the metabolism of arachidonic acid, reduces the amount of prostaglandins in the focus of inflammation. In rheumatic diseases, the anti-inflammatory and analgesic effect of diclofenac significantly reduces the severity of pain, morning stiffness, and joint swelling, which improves the functional state of the joint. In case of injuries, in the postoperative period, diclofenac reduces pain and inflammatory edema.

Pharmacokinetics

Suction

After intramuscular use of diclofenac, its absorption begins immediately. The maximum plasma concentration (Cmax), with an average value of about 2.5 µg / ml (8 µmol / L), is reached after about 20 minutes. The amount of Active ingredient absorbed is linearly dependent on the dose of the drug. The area under the concentration-time curve (AUC) after intramuscular use of diclofenac is approximately 2 times greater than after oral or rectal use, since in the latter cases about half of the amount of diclofenac is metabolized during the” first pass ” through the liver. With subsequent use of the drug, the pharmacokinetic parameters do not change. If the recommended intervals between drug use are observed, no accumulation is observed.

Distribution

The relationship with serum proteins is 99.7%, mainly with albumins (99.4%). The apparent volume of distribution is 0.12-0.17 l / kg. Diclofenac penetrates the synovial fluid, where its maximum concentration is reached 2-4 hours later than in the blood plasma. The apparent half-life (half-life) of synovial fluid is 3-6 hours. 2 hours after reaching the maximum concentration in blood 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 by 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. The isoenzyme CYP2C9 is involved in the metabolism of the drug.

Deduction

The total systemic plasma clearance of diclofenac is 263 ± 56 ml/min. The final 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 ‘ – methoxydiclofenac, has a longer half-life, but this metabolite is completely inactive. About 60% of the dose of the drug is excreted through the kidneys in the form of glucuronic conjugates of the unchanged Active ingredient, 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 is excreted as metabolites in the bile.

Pharmacokinetics in certain groups of patients

The pharmacokinetic parameters of diclofenac in elderly patients do not change. In patients with impaired renal function, accumulation of unchanged Active ingredient is not observed if the recommended dosage regimen is observed. When creatinine clearance is less than 10 ml/min, the calculated steady-state concentrations of diclofenac hydroxymetabolites are approximately 4 times higher than in healthy volunteers, and the metabolites are excreted exclusively in the bile. In patients with chronic hepatitis or compensated cirrhosis of the liver, the pharmacokinetics of diclofenac are similar to those in patients without liver disease. Diclofenac passes into breast milk.

Indications

For short-term treatment of pain of various origins, moderate intensity:

• diseases of the musculoskeletal system (rheumatoid arthritis, psoriatic, juvenile chronic arthritis, ankylosing spondylitis; gouty arthritis, rheumatic soft tissues, osteoarthritis of the peripheral joints and spine (including radicular syndrome);
• lumbago, sciatica, neuralgia;
• algomenorrhea, inflammatory processes of the pelvic organs, including adnexitis;
• post-traumatic pain syndrome, accompanied by inflammation;
• postoperative pain.

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.

Use during pregnancy and lactation

The drug is contraindicated during pregnancy (see the section “Contraindications”). There is no information on the use of Diclofenac during pregnancy. Diclofenac should not be taken during breastfeeding (see section “Contraindications”). Diclofenac passes into breast milk.

Contraindications

Hypersensitivity (including to other NSAIDs or auxiliary components), erosive and ulcerative lesions of the gastrointestinal tract (in the acute phase), bleeding from the gastrointestinal tract, inflammatory bowel diseases, severe liver failure, acute liver disease, severe renal failure (creatinine clearance less than 30 ml/min), hyperkalemia, complete or incomplete acetylsalicylic acid intolerance syndrome (rhinosinusitis, urticaria, nasal polyps, bronchial asthma that occurs when taking acetylsalicylic acid or other NSAIDs), hematopoietic disorders, hemostasis disorders (including hemophilia), pregnancy, children (under 18 years of age), lactation, the period after coronary artery bypass grafting, with an increased risk of arterial thrombosis and thromboembolism, clinically confirmed coronary heart disease, diseases of the peripheral arteries and blood vessels of the brain, chronic heart failure, NYHA functional class II-IV, uncontrolled arterial hypertension.

With caution

Edematous syndrome, peripheral arterial diseases, dyslipidemia, diabetes mellitus, anemia, bronchial asthma, defects in the hemostatic system, with a risk of cardiovascular thrombosis (including myocardial infarction and stroke), renal failure (creatinine clearance 30-60 ml/min), alcoholism, erosive and ulcerative diseases of the gastrointestinal tract without exacerbation, Helicobacter pylori infection, diverticulitis, condition after extensive surgical interventions, induced porphyria, advanced age, smoking, severe somatic diseases, systemic connective tissue diseases, long-term use of nonsteroidal anti-inflammatory drugs.

Caution should be exercised when using in patients with seasonal allergic rhinitis, swelling of the nasal mucosa (including nasal polyps), chronic infectious diseases of the respiratory tract (especially associated with allergic rhinitis-like symptoms). Special care should be taken when using diclofenac in patients receiving drugs that increase the risk of gastrointestinal bleeding: systemic glucocorticosteroids (including prednisone), anticoagulants (including warfarin), antiplatelet agents (including acetylsalicylic acid, clopidogrel) or selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline).

Side effects

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

From the gastrointestinal tract: Often – epigastric pain, nausea, vomiting, diarrhea, dyspepsia, flatulence, anorexia, increased activity of aminotransferases; rarely – gastritis, proctitis, bleeding from the gastrointestinal tract (vomiting with blood, melena, diarrhea with blood), gastrointestinal ulcers (with or without bleeding or perforation), hepatitis, jaundice, liver dysfunction; very rarely-stomatitis, glossitis, esophagitis, non – specific hemorrhagic colitis, exacerbation of ulcerative colitis or Crohn’s disease, constipation, pancreatitis, fulminant hepatitis, hepatorenal syndrome.

From the nervous system: Often-headache, dizziness; rarely-drowsiness; very rarely-sensitivity disorders (including paresthesia), memory disorders, tremor, convulsions, anxiety, cerebrovascular disorders, aseptic meningitis, disorientation, depression, insomnia, “nightmare” dreams, irritability, mental disorders.

From the sensory organs: Often-vertigo; very rarely – visual impairment (blurred vision, diplopia), hearing disorders, tinnitus, impaired taste sensations.

From the skin: Often-skin rash; rarely-urticaria; very rarely-bullous rashes, erythema, including multiforme and Stevens-Johnson syndrome, Lyell’s syndrome, exfoliative dermatitis, itching, hair loss, photosensitization, purpura, including allergic.

From the genitourinary system: Very rarely – acute renal failure, hematuria, proteinuria, interstitial nephritis, nephrotic syndrome, papillary necrosis. Hematopoietic disorders: Very rare – thrombocytopenia, leukopenia, hemolytic and aplastic anemia, agranulocytosis, eosinophilia.

From the respiratory system: Rarely-bronchial asthma (including shortness of breath), cough, laryngeal edema; very rarely – pneumonitis.

From the cardiovascular system: Very rarely-palpitations, chest pain, increased blood pressure, vasculitis, heart failure, myocardial infarction. Allergic reactions: Rarely-anaphylactic / anaphylactoid reactions, including a marked decrease in blood pressure and shock; very rarely-angioedema (including the face).

Other: Often-irritation at the injection site; very rarely-abscess at the injection site; rarely-swelling.

Interaction

Increases plasma concentrations of digoxin, methotrexate, lithium and cyclosporine. Reduces the effect of diuretics, increases the risk of hyperkalemia against the background of potassium-sparing diuretics; against the background of anticoagulants, thrombolytics (alteplase, streptokinase, urokinase) – the risk of bleeding (more often from the gastrointestinal tract). Reduces the effects of antihypertensive and hypnotic medications.

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 concentration of diclofenac in the blood.

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

Concomitant use with ethanol, colchicine, corticotropin, selective serotonin reuptake inhibitors, and St. John’s wort increases the risk of gastrointestinal bleeding. Diclofenac enhances the action 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 it is not recommended to take diclofenac for 8-12 days after the use of mifepristone.

How to take, course of use and dosage

It is administered deep intramuscularly. A single dose for adults is 75 mg (1 ampoule). If necessary, repeated use is possible, but not earlier than after 12 hours. Alternatively, one injection of the drug per day (75 mg) can be combined with other dosage forms of diclofenac (tablets, rectal suppositories), while the total daily dose should not exceed 150 mg. The duration of use is not more than 2 days, if necessary, then switch to oral or rectal use of diclofenac.

Overdose

Symptoms: Vomiting, dizziness, headache, shortness of breath, blurred consciousness, in children-myoclonic seizures, nausea, vomiting, abdominal pain, bleeding, liver and kidney function disorders, respiratory depression, coma.

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

Description

Transparent colorless or slightly yellowish liquid with a slight specific smell.

Special instructions

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

Influence on the ability to drive vehicles and mechanisms

Patients suffering from dizziness and other disorders of the central nervous system should refrain from driving and working with dangerous mechanisms during treatment.

Form of production

Solution for intramuscular use of 25 mg / ml. 3 ml in ampoules made of low-density polyethylene or polypropylene, or in ampoules made of colorless or painted glass. 5 or 10 ampoules of low-density polyethylene or polypropylene together with the instructions for use in a pack of cardboard.

5 ampoules of glass in a contour cell package made of polyvinyl chloride film with polymer film or with aluminum foil varnished, or without polymer film and aluminum foil varnished, or in a (pre-made) form of cardboard with cells for laying ampoules.

1 or 2 contour cell packages or forms made of cardboard with glass ampoules together with instructions for use and ampoule scarifier, or without ampoule scarifier in a pack of cardboard.

Storage conditions

At a temperature not exceeding 25 °C. Keep out of reach of children.

Shelf

life is 2 years. Do not use after the expiration date!

Active ingredient

Diclofenac

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection