Diclofenac, 25 mg/ml 3 ml 5 pcs

Pharmgroup:

NSAIDs.

Pharmacological action:

Penylacetic acid derivative; anti-inflammatory, analgesic and antipyretic effect.

Inhibiting COX1 and COX2 indiscriminately, disrupts arachidonic acid metabolism, reduces the amount of Pg in the focus of inflammation.

The drug is most effective for pain of inflammatory nature. Like all NSAIDs, the drug has antiaggregant activity.

Pharmacokinetics:

Absorption is rapid and complete, food slows the rate of absorption. After oral administration of 50 mg, Cmax is 1.5 mcg/ml, TCmax is 2-3 h.

Diclofenac prolonged action: as a result of slow release of the drug, Cmax in plasma is lower than that produced by administration of short-acting drugs; however, it remains high for a long time after administration.

Cmax is 0.5-1 mcg/ml, TCmax is 5 h after administration of 100 mg sustained release tablets.
After 75 mg IV drip administration, Cmax is 1.9 mcg/ml (5.9 µmol/L). After intravenous administration, Cmax is 2.5 µg/mL (8 µmol/L), TCmax is 20 min.

With rectal administration, TCmax is 30 min.
Plasma concentration is in linear relationship to the amount of dose administered.

No changes in pharmacokinetics of diclofenac on repeated administration. It does not cumulate if the recommended interval between meals is observed.

The bioavailability is 50%. Binding with plasma proteins is more than 99% (most of it is bound with albumin).

Transfers to breast milk, synovial fluid; Cmax in synovial fluid is observed 2-4 hours later than in plasma.

The T1/2 from synovial fluid is 3-6 h (the drug concentrations in synovial fluid are higher 4-6 h after administration than in plasma and remain higher for 12 h).

50% of the drug is metabolized during “first passage” through the liver; AUC is half as much after oral administration of the drug as after parenteral administration of the same dose.

Metabolism occurs as a result of multiple or single hydroxylation and conjugation with glucuronic acid. The CYP2C9 isoenzyme is also involved in the metabolism of the drug.

The pharmacological activity of metabolites is less than that of diclofenac.

The systemic clearance is 260 ml/min. T1/2 from plasma is 1-2 hours. 60% of the administered dose is excreted as metabolites through the kidneys; less than 1% is excreted unchanged, the rest of the dose is excreted as metabolites in the bile.

In patients with significant renal insufficiency (CKD less than 10 ml/min) excretion of metabolites in bile is increased, while there is no increase of their concentrations in blood.

In patients with chronic hepatitis or compensated liver cirrhosis pharmacokinetic parameters do not change.

Indications

Inflammatory and degenerative diseases of the musculoskeletal system:

Rheumatoid, psoriatic, juvenile chronic arthritis, ankylosing spondylitis (Behterev’s disease); gouty arthritis, rheumatic soft tissue lesions, osteoarthritis of peripheral joints and spine (including.

lumbago, sciatica, neuralgia;

algodysmenorrhea, pelvic inflammatory processes, including. adnexitis;

post-traumatic pain syndrome accompanied by inflammation;

renal colic;

postoperative pain.

Active ingredient

Composition

Composition per 1 ml of the drug:

Active substance:

Diclofenac sodium 25.0 mg;

Associates:

Benzyl alcohol,

Sodium metabisulfite,

Mannitol,

How to take, the dosage

In order to reduce the risk of adverse events, it is recommended that the drug be administered at the lowest effective dose for the shortest period of time necessary to relieve symptoms.

In order to avoid damage to the nerve or other tissues at the injection site, the instructions for intramuscular injection should be followed precisely.

The injection solution is injected deeply intramuscularly (into the upper outer quadrant of the gluteal region). A single dose for adults is 75 mg (1 ampoule). If necessary, a second injection is possible, but not earlier than 12 hours later. The second injection should be given in the opposite gluteal area.

The maximum recommended daily dose of the drug Diclofenac solution for intramuscular injection is 150 mg. The duration of use is not more than 2 days; if necessary, further shift to oral or rectal use of diclofenac.

One ampoule of 75 mg of the drug can be combined with other diclofenac dosage forms (enteric-soluble tablets and rectal suppositories); however, it must be taken into account that the maximum daily dose of diclofenac must not exceed 150 mg.

Interaction

Diclofenac may increase the toxic effects of cyclosporine on the kidneys.

When concomitant use with anticoagulants, regular monitoring of blood clotting is required.

When using Diclofenac concomitantly with digoxin, phenytoin or lithium preparations plasma concentrations of these drugs may increase; with diuretics and hypotensive agents with potassium-saving diuretics – possible development of hyperkalemia; with acetylsalicylic acid – decrease of plasma concentration of diclofenac and increased risk of side effects.

When using methotrexate for 24 hours before or after taking Diclofenac may increase the concentration of methotrexate and its toxic effect.

Diclofenac can cause hypo- or hyperglycemia, therefore concomitant use with hypoglycemic agents requires control of blood glucose concentration.

Special Instructions

The risk of adverse reactions with diclofenac increases with increasing dose and duration of treatment.

In order to reduce the risk of adverse events, the drug should be used in the lowest effective dose for the shortest period necessary to relieve symptoms.

When using the drug regularly, periodic assessment of the need for symptom relief, response to ongoing treatment, and timely dose adjustments should be made.

Gastrointestinal tract involvement

When using diclofenac, bleeding or gastrointestinal ulcers/perforations have been reported, in some cases with fatal outcome.

These events can occur at any time when using the drugs in patients with or without prior symptoms and a history of serious gastrointestinal disease.

In elderly patients, such complications can have serious consequences. If patients receiving diclofenac develop bleeding or gastrointestinal ulcers, the drug should be discontinued.

In order to reduce the risk of gastrointestinal toxicity in patients with gastrointestinal ulcers, especially those with a history of bleeding or perforation, and in elderly patients, the drug should be used in the lowest effective dose.

Patients at increased risk of gastrointestinal complications, as well as patients receiving low-dose therapy with acetylsalicylic acid (Aspirin), should take gastroprotective agents (proton pump inhibitors or misoprostol) or other medications to reduce the risk of GI adverse effects.

Patients with a history of gastrointestinal damage, especially the elderly, should tell their physician about any abdominal symptoms.

Patients with bronchial asthma

An exacerbation of bronchial asthma (NSAID intolerance/ bronchial asthma triggered by taking NSAIDs), Quincke’s edema and urticaria are most commonly seen in patients with bronchial asthma, seasonal/p>

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, pruritus or urticaria) special caution should be exercised when using diclofenac (readiness for resuscitation measures).

Skin reactions

Serious dermatologic reactions such as exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, in some cases with fatal outcome, against the background of diclofenac use have been very rarely reported.

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, mucosal lesions or other symptoms of hypersensitivity, the drug should be discontinued.

In rare cases anaphylactic/anaphylactoid reactions may develop in patients who are not allergic to diclofenac.

Impacts on the liver

As during the use of diclofenac increased activity of one or more liver enzymes may be noted, during long-term therapy with the drug, monitoring of liver function is indicated as a precautionary measure.

If liver function abnormalities persist and progress or signs of liver disease or other symptoms (e.g., eosinophilia, rash, etc.) occur, the drug should be stopped.

Please note that hepatitis with diclofenac may occur without prodromal signs.

Renal effects

With diclofenac therapy it is recommended to monitor renal function in patients with hypertension, impaired heart or renal function, the elderly, patients receiving diuretics or other

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, such as before and after massive surgical interventions.

After discontinuation of therapy with the drug, normalization of renal function to baseline values is usually noted.

Cardiovascular effects

Therapy with NSAIDs, including diclofenac, especially long-term and high-dose therapy, may be associated with a small increase in the risk of serious cardiovascular thrombotic complications (including myocardial infarction and stroke).

Patients with cardiovascular disease and high cardiovascular risk (e.g., those with arterial hypertension, hyperlipidemia, diabetes mellitus, smokers)

Patients The drug should be prescribed only after careful consideration and should be used with extreme caution, at the lowest effective dose with the shortest possible duration of treatment, because the risk of thrombotic complications increases with increasing dose and duration of treatment.

In long-term therapy (more than 4 weeks) the daily dose of diclofenac in these patients should not exceed 100 mg. The effectiveness of treatment and the patient’s need for symptomatic therapy should be periodically evaluated, especially when the duration of therapy is more than 4 weeks.

The patient should be instructed to seek immediate medical attention when the first symptoms of thrombotic disorders appear (e.g., chest pain, shortness of breath, weakness, speech disorders). Effects on the hematopoietic system

Diclofenac may temporarily inhibit platelet aggregation. Therefore, in patients with hemostasis disorders it is necessary to carry out careful monitoring of the relevant laboratory parameters.

In long-term use of diclofenac it is recommended to perform regular clinical peripheral blood tests.

Masking signs of an infectious process

The anti-inflammatory effects of diclofenac may make it difficult to diagnose infectious processes.

Combined use with other NSAIDs

Do not use diclofenac simultaneously with other NSAIDs, including COX-2 selective inhibitors due to the risk of increased adverse events.

Impact on female fertility

Diclofenac may have adverse effects on female fertility, so it is not recommended for women who want to become pregnant.

In women who have difficulty conceiving (including those undergoing tests), discontinuation of diclofenac should be considered.

The ingredient sodium metabisulfite may rarely cause severe hypersensitivity reactions and bronchospasm.

Information for patients on a sodium-controlled diet

The sodium content of one ampoule (3 ml) of Diclofenac Injection Solution is less than 1 mmol (23 mg), which is almost “sodium-free.

Synopsis

Features

Contraindications

Hypersensitivity (including to other NSAIDs), complete or incomplete combination of bronchial asthma, recurrent nasal and paranasal sinus polyposis and ASA or other intolerances.

NSAIDs (including history), erosive-ulcerative lesions of the gastrointestinal tract and duodenum, active gastrointestinal bleeding, inflammatory bowel disease, severe hepatic and cardiac failure;

Post aortocoronary bypass surgery; severe renal impairment (CKR less than 30 ml/min), advanced renal disease, active liver disease, confirmed hyperkalemia,

Pregnancy (III trimester), lactation, children (under 14 years of age – for enteric coated tablets 50 mg and rectal suppositories 50 mg, under 18 years of age – for sustained release tablets and suppositories 100 mg).

In rectal administration (additionally): proctitis.

For FP containing lactose (optionally): hereditary lactose intolerance, impaired glucose-galactose absorption, lactase deficiency.

With caution.

Peptic ulcer disease, ulcerative colitis, Crohn’s disease, liver disease in anamnesis, hepatic porphyria, COPD, CHF, arterial hypertension, significant reduction of the blood circulation (including

Elderly patients (including those treated with diuretics, frail patients, and underweight patients),

Bronchial asthma, concomitant use of GCS (including prednisolone), anticoagulants (including warfarin), anticonvulsantsanticoagulants (including warfarin), antiplatelet agents (including ASA, clopidogrel), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline),

IBS, cerebrovascular disease, dyslipidemia/hyperlipidemia,

Diabetes mellitus, peripheral arterial disease, smoking, CKD (IQ 30-60 ml/min), presence of Helicobacter pylori infection, long-term use of NSAIDs, alcoholism, severe medical conditions.

Side effects

Digestive system disorders: nausea, vomiting, epigastric pain, anorexia, flatulence, constipation, gastritis up to erosive with bleeding, increased transaminase activity, drug-induced hepatitis, pancreatitis.

Urinary system disorders: interstitial nephritis.

CNS disorders: headache, dizziness, disorientation, agitation, insomnia, irritability, fatigue, aseptic meningitis.

Respiratory system: bronchospasm.

Hematopoietic system: anemia, thrombocytopenia, leukopenia, agranulocytosis.

Dermatological reactions: exanthema, erythema, eczema, hyperemia, erythrodermia, photosensitization.

Allergic reactions: erythema multiforme, Lyell’s syndrome, Stevens-Johnson syndrome, anaphylactic reactions, including shock.

Local reactions: burning, infiltrate formation, necrosis of adipose tissue possible at the injection site.

Others: fluid retention in the body, edema, increased BP.

Overdose

Symptoms:

Gastrointestinal bleeding, diarrhea, vomiting, epigastric pain, dizziness, tinnitus, lethargy, seizures, rarely increased BP, acute renal failure, hepatotoxic effects, respiratory depression, coma.

Treatment:

Gastric lavage, activated charcoal, symptomatic therapy aimed at eliminating increased BP, impaired renal function, seizures, gastrointestinal irritation, respiratory depression.

Forced diuresis and hemodialysis are ineffective (due to significant binding to proteins and intense metabolism).

Pregnancy use

Contraindicated.

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