Diclofenac Bufus (Solution) Instructions for Use

Marketing Authorization Holder

Obnovlenie Pfc, JSC (Russia)

ATC Code

M01AB05 (Diclofenac)

Active Substance

Diclofenac (Rec.INN WHO registered)

Dosage Form

Diclofenac Bufus

Solution for intramuscular injection 75 mg/3 ml: amp. 5, 10, or 100 pcs.

Dosage Form, Packaging, and Composition

3 ml – ampoules (5) – carton packs.
3 ml – ampoules (10) – carton packs.
3 ml – ampoules (10) – packs (10) – carton boxes.

Clinical-Pharmacological Group

NSAID

Pharmacotherapeutic Group

NSAID

Pharmacological Action

Diclofenac has anti-inflammatory, analgesic, and antipyretic effects.

By non-selectively inhibiting cyclooxygenase 1 and 2, it disrupts arachidonic acid metabolism and reduces the amount of prostaglandins at the site of inflammation.

In rheumatic diseases, the anti-inflammatory and analgesic effect of diclofenac contributes to a significant reduction in the severity of pain, morning stiffness, and joint swelling, which improves the functional state of the joint.

In injuries and in the postoperative period, Diclofenac reduces pain and inflammatory edema.

Pharmacokinetics

The time to reach C_max after intramuscular administration of a 75 mg dose is 15-30 minutes. The C_max value is 1.9-4.8 (average 2.7) µg/ml.

Three hours after administration, the plasma concentration averages 10% of the maximum.

Plasma protein binding is more than 99% (mostly bound to albumin).

Metabolism occurs as a result of multiple or single hydroxylation and conjugation with glucuronic acid.

The enzyme system P450 CYP2C9 is involved in the metabolism of the drug.

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

Systemic clearance is 350 ml/min, V_d is 550 ml/kg.

T_1/2 from plasma is 2 hours.

65% of the administered dose is excreted by the kidneys as metabolites; less than 1% is excreted unchanged, the remainder of the dose is excreted as metabolites in the bile.

In patients with severe renal failure (creatinine clearance less than 10 ml/min), the excretion of metabolites in the bile increases, but no increase in their blood concentration is observed.

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

Diclofenac penetrates into breast milk.

Indications

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

• Musculoskeletal disorders (rheumatoid arthritis, psoriatic arthritis, juvenile chronic arthritis, ankylosing spondylitis; gouty arthritis, rheumatic soft tissue lesions, osteoarthritis of peripheral joints and spine (including with radicular syndrome);
• Lumbago, sciatica, neuralgia;
• Dysmenorrhea, inflammatory processes of the pelvic organs, incl. adnexitis;
• Post-traumatic pain syndrome accompanied by inflammation;
• Postoperative pain.

ICD codes

Dosage Regimen

Administer the solution by deep intramuscular injection only.

The standard adult dose is 75 mg as a single injection, equivalent to the contents of one 3 ml ampoule.

For repeated administration, maintain a minimum interval of 12 hours between injections.

Limit the total duration of intramuscular treatment to a maximum of 2 days.

If continued analgesic or anti-inflammatory therapy is required beyond two days, transition to an oral or rectal formulation of diclofenac.

Always use the lowest effective dose for the shortest possible duration to control symptoms.

Select the injection site carefully, avoiding nerves, blood vessels, and other sensitive tissues.

Do not administer this formulation to children or adolescents under 18 years of age.

For patients with mild to moderate renal impairment, exercise caution and monitor renal function.

In elderly patients, initiate treatment at the lower end of the dosing range.

Adverse Reactions

To reduce the risk of adverse events, the minimum effective dose should be used for a short course.

Gastrointestinal tract: more than 1% – abdominal pain, feeling of abdominal bloating, diarrhea, indigestion, nausea, constipation, flatulence, increased levels of ‘liver’ enzymes, peptic ulcer with possible complications (bleeding, perforation), gastrointestinal bleeding; less than 1% – vomiting, jaundice, melena, appearance of blood in the stool, esophageal lesions, aphthous stomatitis, dry mouth and mucous membranes, hepatitis (possibly fulminant), liver necrosis, cirrhosis, hepatorenal syndrome, change in appetite, pancreatitis, cholecystopancreatitis, colitis.

Nervous system: more than 1% – headache, dizziness; less than 1% – sleep disturbance, drowsiness, depression, irritability, aseptic meningitis (more often in patients with systemic lupus erythematosus and other systemic connective tissue diseases), convulsions, weakness, disorientation, nightmares, feeling of fear.

Sensory organs: more than 1% – tinnitus; less than 1% – blurred vision, diplopia, taste disturbance, reversible or irreversible hearing loss, scotoma.

Skin: more than 1% – skin itching, skin rash; less than 1% – alopecia, urticaria, eczema, toxic dermatitis, multiforme exudative erythema, incl. Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), increased photosensitivity, petechiae.

Urinary system: more than 1% – fluid retention; less than 1% – nephrotic syndrome, proteinuria, oliguria, hematuria, interstitial nephritis, papillary necrosis, acute renal failure, azotemia.

Hematopoietic organs and immune system: less than 1% – anemia (including hemolytic and aplastic anemia), leukopenia, thrombocytopenia, eosinophilia, agranulocytosis, thrombocytopenic purpura, worsening of infectious processes (development of necrotizing fasciitis, pneumonia).

Respiratory system: less than 1% – cough, bronchospasm, laryngeal edema, pneumonitis.

Cardiovascular system: less than 1% – increased blood pressure, congestive heart failure, extrasystole, chest pain.

Allergic reactions: less than 1% – anaphylactoid reactions, anaphylactic shock (usually develops rapidly), swelling of the lips and tongue, allergic vasculitis.

Local reactions with intramuscular injection: burning, infiltrate, aseptic necrosis, necrosis of adipose tissue.

Contraindications

Hypersensitivity (including to other NSAIDs or excipients), erosive and ulcerative lesions of the gastrointestinal tract (in the acute phase), gastrointestinal bleeding, inflammatory bowel diseases, severe hepatic failure, liver diseases in the acute period, severe renal failure (creatinine clearance less than 30 ml/min), hyperkalemia, complete or incomplete acetylsalicylic acid intolerance syndrome (rhinosinusitis, urticaria, nasal mucosal polyps, bronchial asthma, occurring when taking acetylsalicylic acid or another NSAID), blood formation disorders, hemostasis disorders (including hemophilia), pregnancy, childhood (up to 18 years), lactation period, period after coronary artery bypass grafting.

With caution. Ischemic heart disease, cerebrovascular diseases, congestive heart failure, arterial hypertension, edematous syndrome, peripheral artery diseases, dyslipidemia, diabetes mellitus, anemia, bronchial asthma, renal failure (creatinine clearance less than 60 ml/min), alcoholism, erosive and ulcerative diseases of the gastrointestinal tract outside the acute phase, diverticulitis, condition after extensive surgical interventions, inducible porphyria, elderly age, smoking, severe somatic diseases, systemic connective tissue diseases, long-term use of non-steroidal anti-inflammatory drugs.

Use in Pregnancy and Lactation

Contraindicated: pregnancy, lactation period.

Use in Hepatic Impairment

Contraindicated: severe hepatic failure, liver diseases in the acute period.

Use in Renal Impairment

Contraindicated: severe renal failure (creatinine clearance less than 30 ml/min). With caution: renal failure (creatinine clearance less than 60 ml/min).

Pediatric Use

Contraindicated: childhood (up to 18 years).

Geriatric Use

With caution: elderly age.

Special Precautions

Patients using the drug should refrain from activities requiring increased attention and rapid mental and motor reactions, and from consuming alcohol.

Overdose

Symptoms: vomiting, dizziness, headache, shortness of breath, clouding of consciousness, in children – myoclonic convulsions, nausea, vomiting, abdominal pain, bleeding, impaired liver and kidney function.

Treatment: symptomatic therapy, forced diuresis. Hemodialysis is not very effective.

Drug Interactions

Increases the plasma concentration of digoxin, methotrexate, lithium preparations, and cyclosporine.

Reduces the effect of diuretics; against the background of potassium-sparing diuretics, the risk of hyperkalemia increases; against the background of anticoagulants, thrombolytic agents (alteplase, streptokinase, urokinase) – the risk of bleeding (more often from the gastrointestinal tract). Reduces the effects of antihypertensive and hypnotic agents.

Increases the likelihood of side effects of other non-steroidal anti-inflammatory drugs and glucocorticosteroid agents (bleeding in the gastrointestinal tract), the toxicity of methotrexate and the nephrotoxicity of cyclosporine.

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.

Cefamandole, cefoperazone, cefotetan, valproic acid, and plicamycin increase the frequency of hypoprothrombinemia.

Cyclosporine and gold preparations enhance the effect of diclofenac on prostaglandin synthesis 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 bleeding in the gastrointestinal tract.

Diclofenac enhances the effect of drugs that cause photosensitization.

Drugs that block tubular secretion increase the plasma concentration of diclofenac, thereby increasing its toxicity.

Storage Conditions

In a light-protected place at a temperature not exceeding 25°C (77°F).

Keep out of reach of children.

Shelf Life

Shelf life. 2 years. Do not use after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.