Diclofenac solution 25 mg/ml 3 ml ampoules, 5 pcs.

Composition

Composition per 1 ml of the drug:

Active ingredient: 

Diclofenac sodium 25.0 mg;

Auxiliary substances: 

Benzyl alcohol,

Sodium metabisulfite,

Mannitol,

Sodium hydroxide,

Propylene Glycol,

Water for injection.

Pharmacological action

Pharmaceutical Group:

NSAIDs.

Pharmaceutical action: 

NSAIDs, a derivative of phenylacetic acid; has anti-inflammatory, analgesic and antipyretic effects.

By indiscriminately inhibiting COX 1 and COX 2, it disrupts arachidonic acid metabolism and reduces the amount of Pg in the inflammatory focus.

It is most effective for inflammatory pain. Like all NSAIDs, the drug has antiplatelet activity.

Pharmacokinetics:

Absorption-fast and complete, food slows down the rate of absorption. After oral administration of 50 mg, Cmax – 1.5 mcg / ml, TCmax-2-3 hours.

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

Cmax-0.5-1 mcg / ml, TCmax-5 hours after taking 100 mg of long-acting tablets. After intravenous drip administration of 75 mg, Cmax is 1.9 mcg / ml (5.9 mmol / l). After intravenous administration, Cmax is 2.5 mcg / ml (8 mmol / L), TCmax is 20 min.

With rectal administration, TCmax is 30 minutes. The plasma concentration is linearly dependent on the amount of the administered dose.

There were no changes in the pharmacokinetics of diclofenac during repeated administration. It does not accumulate if the recommended interval between meals is observed.

Bioavailability – 50%. Binding to plasma proteins is more than 99% (most of them are bound to albumins).

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

T1 / 2 from synovial fluid – 3-6 hours (concentrations of the drug in synovial fluid 4-6 hours after its administration are higher than in plasma, and remain higher for another 12 hours).

50% of the drug is metabolized during the” first pass ” through the liver; AUC is 2 times less after oral administration of the drug than after parenteral administration of the same dose.

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

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

Systemic clearance is 260 ml / min. T1 / 2 from plasma – 1-2 h.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 severe renal insufficiency (creatinine clearance less than 10 ml / min), the excretion of metabolites in the bile increases, while no increase in their concentration in the blood is observed.

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

Indications

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

Inflammatory and degenerative diseases of the musculoskeletal system:

rheumatoid, psoriatic, juvenile chronic arthritis, ankylosing spondylitis (Bechterew’s disease); 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;

renal colic;

postoperative pain.

Use during pregnancy and lactation

Contraindicated.

Contraindications

Hypersensitivity (including to other NSAIDs), complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and paranasal sinuses and intolerance to ASA or other

NSAIDs (including in history), erosive and ulcerative lesions of the gastrointestinal tract and 12 duodenal ulcer, active gastrointestinal bleeding, inflammatory bowel disease, severe liver or heart failure;

after the coronary artery bypass surgery; severe renal insufficiency (CC less than 30 ml/min), progressive kidney disease, active liver disease, confirmed hyperkalemia,

pregnancy (III trimester), lactation, children’s age (up to 14 years – designed for tablets, enteric coated tablets 50 mg, and rectal suppository of 50 mg to 18 years – for tablets of prolonged action and suppositories 100 mg).

For rectal use (optional): proctitis.

For medicinal products containing lactose (optional): hereditary lactose intolerance, glucose-galactose malabsorption, lactase deficiency.

With caution.

Gastric ulcer and 12 duodenal ulcer, ulcerative colitis, Crohn’s disease, liver disease, a history of hepatic porphyria, chronic renal failure, CHF, hypertension, a significant decrease in BCC (including after extensive surgery),

elderly patients (including receiving diuretics, debilitated patients and those with a low body weight),

bronchial asthma, concomitant use of corticosteroids (e. g. prednisone), anticoagulants (including warfarin), antiplatelet agents (including ASA, clopidogrel), selective inhibitors of serotonin reuptake (including citalopram, fluoxetine, paroxetine, and sertraline),

ischemic heart disease, cerebrovascular disease, dyslipidemia/hyperlipidemia,

diabetes mellitus, peripheral artery disease, Smoking, chronic renal failure (KK 30-60 ml/min), the presence of Helicobacter pylori infection, prolonged use of NSAIDs, alcoholism, severe somatic diseases.

Side effects

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

From the urinary system: interstitial nephritis.

From the central nervous system: headache, dizziness, disorientation, agitation, insomnia, irritability, fatigue, aseptic meningitis.

Respiratory system disorders: bronchospasm.

From the hematopoietic system: anemia, thrombocytopenia, leukopenia, agranulocytosis.

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

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

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

Other services: fluid retention in the body, edema, increased blood pressure.

Interaction

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

When used concomitantly with anticoagulants, regular monitoring of blood clotting parameters is necessary.

Concomitant use of Diclofenac with digoxin, phenytoin or lithium preparations may increase the plasma concentrations of these drugs; with diuretics and antihypertensive

agents, the effect of these drugs may decrease; with potassium-sparing diuretics, hyperkalemia may develop; with acetysalicylic acid, a decrease in the concentration of diclofenac in blood plasma and an increased risk of side effects.

When using methotrexate for 24 hours before or after taking Diclofenac, it is possible to increase the concentration of methotrexate and increase its toxic effect.

Diclofenac can cause hypo – or hyperglycemia, so when used concomitantly with hypoglycemic agents, monitoring of blood glucose concentration is required.

How to take, course of administration and dosage

In order to reduce the risk of adverse events, the drug is recommended to be used 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, you should strictly follow the instructions for intramuscular injection.

The injection solution is administered deep intramuscularly (in the upper outer quadrant of the gluteal region). A single dose for adults is 75 mg (1 ampoule). If necessary, repeated administration is possible, but not earlier than after 12 hours. The second injection should be made in the opposite buttock area.

The maximum recommended daily dose of Diclofenac solution for intramuscular administration is 150 mg. The duration of use is not more than 2 days, if necessary, then switch to oral or rectal use of diclofenac.

One ampoule of 75 mg of the drug can be combined with other dosage forms of diclofenac (enteric coated tablets, rectal suppositories), while attention should be paid to the fact that the maximum daily dose of diclofenac should not exceed 150 mg.

Overdose

Symptoms: 

gastrointestinal bleeding, diarrhea, vomiting, epigastric pain, dizziness, tinnitus, lethargy, convulsions, rarely-increased blood pressure, acute renal failure, hepatotoxic effect, respiratory depression, coma.

Treatment: 

gastric lavage, activated charcoal, symptomatic therapy aimed at eliminating increased blood pressure, impaired renal function, convulsions, gastrointestinal irritation, respiratory depression.

Forced diuresis and hemodialysis are ineffective (due to significant protein binding and intensive metabolism).

Purpose

Nonsteroidal Anti-inflammatory drug (NSAID)

Description

Transparent from colorless to slightly yellow solution with a weak characteristic smell of benzyl alcohol.

Functional features

Absorption The time to reach the maximum concentration with intramuscular administration at a dose of 75 mg is 15-30 minutes, the maximum concentration is 1.9-4.8 (average 2.7) mcg / ml.3 hours after administration, plasma concentrations are on average 10% of the maximum. Distribution of binding to plasma proteins — more than 99% (most of it binds to albumins). The volume of distribution is 550 ml / 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 from synovial fluid is 3-6 hours.2 hours after reaching the maximum concentration in 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. MetabolismMetabolism occurs as a result of multiple or single hydroxylation and conjugation with glucuronic acid. Cytochrome P450 isoenzyme CYP2C9 is involved in drug metabolism. The pharmacological activity of the metabolites is lower than that of diclofenac. Excretionsystemic clearance is 350 ml/min. The plasma half-life is 2 hours.65% of the administered dose is excreted as metabolites by the kidneys; less than 1% is excreted unchanged, the rest of the dose is excreted as metabolites in the bile. Diclofenac passes into breast milk. Pharmacokinetics in certain groups of patients with severe renal insufficiency (creatinine clearance less than 10 ml/min), the excretion of metabolites in the bile increases, while their concentration in the blood does not increase. In patients with chronic hepatitis or compensated cirrhosis of the liver, the pharmacokinetic parameters of diclofenac do not change.

Complete set

Solution for intramuscular administration of 25 mg / ml.3 ml of the drug in ampoules of colorless glass of hydrolytic class I. A dot and a ring are applied to the ampoule with brown paint.5 ampoules each in a contour cell package made of polyvinyl chloride film and aluminum foil. Contour cell packaging together with the instructions for use is placed in a pack of cardboard.

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 at the lowest effective dose for the shortest period necessary to relieve symptoms.

With regular use of the drug, it is necessary to periodically assess the need for relief of symptoms, response to treatment, and timely dose adjustment.

Damage to the gastrointestinal tract

When using diclofenac, there were such phenomena as bleeding or ulceration/perforation of the gastrointestinal tract, in some cases with a fatal outcome.

These events may occur at any time when the drugs are used in patients with or without previous symptoms and a history of serious gastrointestinal diseases.

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

To reduce the risk of toxic effects on the gastrointestinal tract in patients with ulcerative lesions of the gastrointestinal tract. especially complicated by bleeding or perforation in the anamnesis, as well as in elderly patients, the drug should be used at the minimum effective dose.

Patients with an increased risk of developing gastrointestinal complications, as well as patients receiving low-dose acetylsalicylic acid (Aspirin) therapy, should take gastroprotectors

(proton pump inhibitors or misoprostol) or other medications to reduce the risk of undesirable effects on the gastrointestinal tract.

Patients with a history of gastrointestinal tract involvement, especially the elderly, should inform the doctor about all abdominal symptoms.

Patients with bronchial asthma

Exacerbation of bronchial asthma (NSAID intolerance/NSAID-induced asthma), Quincke’s edema, and urticaria are most commonly reported in patients with bronchial asthma, seasonal

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 care should be taken when using diclofenac (readiness for resuscitation measures).

Skin reactions

Such serious dermatological reactions as exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, in some cases with a fatal outcome, against the background of the use of diclofenac were very rarely observed.

The greatest risk and frequency of severe dermatological reactions were observed in the first month of diclofenac treatment.

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 occur in patients who are not allergic to diclofenac.

Effects on the liver

Since an increase in the activity of one or more liver enzymes may occur during the use of diclofenac, monitoring of liver function is indicated as a precautionary measure during long-term therapy with the drug.

If liver function disorders persist and progress, or if signs of liver disease or other symptoms occur (for example, eosinophilia, rash, etc. ), the drug should be discontinued.

It should be borne in mind that hepatitis against the background of the use of diclofenac can develop without prodromal phenomena.

Effects on the kidneys

Against the background of therapy with diclofenac is recommended to monitor renal function in patients with hypertension, impaired heart function, or kidney disease, elderly patients receiving diuretics or other

drugs affecting renal function and in patients with a significant decrease in the volume of circulating blood plasma of any etiology, for example, in the period before and after a massive surgery.

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

Effects on the cardiovascular system

NSAID therapy, 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 diseases of the cardiovascular system and a high risk of developing diseases of the cardiovascular system (for example, with arterial hypertension, hyperlipidemia, diabetes mellitus, smoking) 

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

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

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

Diclofenac may temporarily inhibit platelet aggregation. Therefore, in patients with hemostatic disorders, it is necessary to carefully monitor the appropriate laboratory parameters.

With prolonged use of diclofenac, it is recommended to conduct regular clinical tests of peripheral blood.

Masking signs of an infectious process

The anti-inflammatory effect of diclofenac can make it difficult to diagnose infectious processes.

Concomitant use with other NSAIDs

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

Impact on women’s fertility

Diclofenac can have a negative effect on women’s fertility, so women who want to get pregnant, diclofenac is not recommended.

Discontinuation of diclofenac should be considered in women who have difficulty conceiving (including those undergoing screening).

Sodium metabisulfite, which is part of the drug, can rarely cause severe hypersensitivity reactions and bronchospasm.

Information for patients on a controlled sodium diet

The sodium content in one ampoule (3 ml) of Diclofenac solution for injection does not exceed 1 mmol (23 mg), i. e. practically “without sodium”.

Form of production

Solution for intramuscular administration

Storage conditions

Store in a dry place protected from light at a temperature not exceeding 25 C. Keep out of reach of children. 

Expiration date

At a temperature of 15 to 25 °C. Keep out of reach of children!

Active ingredient

Diclofenac

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection

Purpose

For adults

Indications

Lumbago, Osteoarthritis, Tendon Inflammation, Swelling after Injuries and operations, Osteoarthritis, Periarthritis, Arthritis, Rheumatoid Arthritis, Adnexitis, Sciatica, Bursitis

Weight

Weight: 41 gr.