INSTRUCTIONS FOR MEDICAL USE

KUPEN

QUPEN

Trade name of the drug: Kupen

Active ingredient (INN): diclofenac sodium

Dosage form: solution for injection

Composition:

Each ml contains:

and active substance: diclofenac sodium 25 mg

in excipients: benzyl alcohol, water for injection.

Description: clear, colorless or yellowish liquid

Pharmacotherapeutic group: non-steroidal anti-inflammatory drug (NSAID).

Code ATH: M01AB05

Pharmacological properties

Diclofenac has anti-inflammatory, analgesic and antipyretic effects. By indiscriminately inhibiting cyclooxygenase 1 and 2, it disrupts the metabolism of arachidonic acid and reduces the amount of prostaglandins at the site of inflammation. In rheumatic diseases, the anti-inflammatory and analgesic effect of diclofenac helps to significantly reduce the severity of pain, morning stiffness, and swelling of the joints, which improves the functional state of the joint. For injuries, in the postoperative period, diclofenac reduces pain and inflammatory swelling.

It has been established that the drug has a strong analgesic effect in moderate to severe pain syndrome. In the presence of inflammation, caused, for example, by injury or surgery, the drug quickly eliminates both spontaneous pain and pain during movement, and also reduces inflammatory swelling of tissues and swelling in the area of the surgical wound.

Pharmacokinetics

The time to reach the maximum concentration when administered intramuscularly at a dose of 75 mg is 15-30 minutes, the value of the maximum concentration is 1.9-4.8 (on average 2.7) mcg/ml. 3 hours after administration, the plasma concentration averages 10% of the maximum.

Communication with plasma proteins is more than 99% (most of it is associated with albumin).

Diclofenac penetrates into the synovial fluid, where maximum concentrations are measured 2 to 4 hours after peak plasma values are reached. The apparent half-life from synovial fluid is 3 to 6 hours. Two hours after peak plasma values are reached, concentrations of the active substance are higher in synovial fluid than in plasma and remain high for up to 12 hours.

Metabolism occurs as a result of multiple or single hydroxylation and conjugation with glucuronic acid. The enzyme system P450 CYP2C9 takes part in the metabolism of the drug. The pharmacological activity of the metabolites is lower than that of diclofenac.

Systemic clearance is 350 ml/min, volume of distribution is 550 ml/kg. The half-life from plasma is 2 hours. 65% of the administered dose is excreted in the form of metabolites by 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 failure (creatinine clearance less than 10 ml/min), the excretion of metabolites in bile increases, but no increase in their concentration in the blood is observed.

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

Diclofenac passes into breast milk.

Indications for use

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 tissue disease,

— osteoarthritis of peripheral joints and spine (including radicular syndrome).

The drug is intended for symptomatic therapy, reducing pain and inflammation at the time of use, does not affect the progression of the disease;

— lumbago, sciatica, neuralgia;

— algodismenorrhea, inflammatory processes of the pelvic organs, incl. adnexitis;

— post-traumatic pain syndrome accompanied by inflammation;

— postoperative pain.

Directions for use and doses

It is administered deeply intramuscularly. Single dose for adults – 75 mg (1 ampoule). If necessary, repeated administration is possible, but not earlier than after 12 hours. When using other dosage forms of diclofenac, the maximum daily dose should not be exceeded — 150 mg.

Duration of use is no more than 2 days, if necessary, then switch to oral or rectal use of diclofenac.

Side effects

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

Often — 1-10%; sometimes 0.1-1%; rarely 0.01-0.1%; very rarely — less than 0.001%, including isolated cases.

From the digestive system:

— often — epigastric pain, nausea, vomiting, diarrhea, dyspepsia, flatulence, anorexia, increased aminotransferase activity;

— rarely — gastritis, proctitis, bleeding from the gastrointestinal tract (vomiting with blood, melena, diarrhea mixed with blood), ulcers of the gastrointestinal tract (with or without bleeding or perforation), hepatitis, jaundice, impaired liver function;

— very rarely — stomatitis, glossitis, damage to the esophagus, diaphragm-like intestinal strictures (nonspecific hemorrhagic colitis, exacerbation of ulcerative colitis or Crohn’s disease), constipation, pancreatitis, fulminant hepatitis.

From the nervous system:

— often — headache, dizziness;

— rarely — drowsiness;

— very rarely — sensory disturbance, incl. paresthesia, memory disorders, tremor, convulsions, anxiety, cerebrovascular disorders, aseptic meningitis, disorientation, depression, insomnia, nightmares, irritability, mental disorders.

From the senses:

— often — vertigo;

— very rarely — visual impairment (blurred vision, diplopia), hearing impairment, tinnitus, impaired sense of taste.

From the urinary system:

— very rarely — acute renal failure, hematuria, proteinuria, interstitial nephritis, nephrotic syndrome, papillary necrosis.

From the hematopoietic organs:

— very rarely — thrombocytopenia, leukopenia, hemolytic and aplastic anemia, agranulocytosis.

Allergic reactions:

— anaphylactic/anaphylactoid reactions, including a pronounced decrease in blood pressure and shock;

— very rarely — angioedema (including the face).

From the cardiovascular system:

— very rarely — palpitations, chest pain, increased blood pressure, vasculitis, heart failure, myocardial infarction.

From the respiratory system:

— rarely — bronchial asthma (including shortness of breath);

— very rarely — pneumonitis.

From the skin:

— often — skin rash;

— rarely — urticaria;

— very rarely — bullous rashes, eczema, incl. multiforme and Stevens-Johnson syndrome, Lyell’s syndrome, exfoliative dermatitis, itching, hair loss, photosensitivity, purpura, incl. allergic.

Local reactions with intramuscular administration :

— burning, infiltration, aseptic necrosis, necrosis of adipose tissue.

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 (ulcerative colitis, Crohn’s disease),
severe liver failure,
liver diseases in the acute period,
severe renal failure (creatinine clearance less than 30 ml/min),
heart failure,
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,
lactation period,
children’s age (up to 18 years),
period after coronary artery bypass surgery.

With caution : coronary heart disease, cerebrovascular diseases, congestive heart failure, arterial hypertension, significant decrease in circulating blood volume (including after major surgery), edema syndrome, peripheral arterial disease, dyslipidemia, diabetes mellitus, anemia, bronchial asthma , renal failure (creatinine clearance less than 60 ml/min), alcoholism, erosive and ulcerative diseases of the gastrointestinal tract without exacerbation, history of liver disease, diverticulitis, condition after major surgical interventions, inducible porphyria, old age, smoking, severe somatic diseases , systemic connective tissue diseases, long-term use of non-steroidal anti-inflammatory drugs, simultaneous use of glucocorticosteroids, anticoagulants, antiplatelet agents, selective serotonin reuptake inhibitors, hyperlipidemia, the presence of Helicobacter pylori infection.

Drug interactions

Increases plasma concentrations of digoxin, methotrexate, lithium 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 (usually from the gastrointestinal tract).

Reduces the effects of antihypertensive and hypnotic drugs.

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 developing nephrotoxic effects of diclofenac.

Anticoagulants. Although clinical studies have not established the effect of the drug on the action of anticoagulants, there are reports of an increased risk of bleeding in patients taking diclofenac and these drugs simultaneously. Therefore, in the case of such a combination of drugs, careful and regular monitoring of patients is recommended.

Antidiabetic drugs. Clinical studies have shown that the drug can be used in conjunction with oral antidiabetic agents and will not change their therapeutic effect. However, there are isolated reports of the development of both hypoglycemia and hyperglycemia, which forced changes in the dose of glucose-lowering drugs during use of the drug.

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

Cyclosporine and gold preparations increase the effect of diclofenac on the synthesis of prostaglandins in the kidneys, which increases nephrotoxicity.

Simultaneous 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 photosensitivity.

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

Antibacterial drugs from the quinolone group – the risk of developing seizures.

special instructions

Patients using the drug must refrain from activities that require increased attention and rapid mental and motor reactions, and alcohol consumption.

Caution is necessary when prescribing the drug to patients with hepatic porphyria, since the drug can provoke attacks of porphyria.

Since prostaglandins play an important role in maintaining renal blood flow, special caution is required when treating patients with impaired cardiac or renal function, elderly patients, patients receiving diuretics, and patients who have a significant decrease in circulating plasma volume of any etiology, for example , in the period before and after massive surgical interventions. In such cases, during use of the drug, as a precaution, regular monitoring of renal function is recommended.

After discontinuation of the drug, renal function is usually restored to its original level.

The use of the drug for all of the above indications is usually limited to a few days. However, if, despite the recommendations for use, the drug is used for an extended period of time, it is recommended, as with long-term use of other NSAIDs, to monitor the composition of the peripheral blood.

The drug, like other NSAIDs, may temporarily inhibit platelet aggregation. Therefore, careful appropriate laboratory monitoring is necessary in patients with hemostasis disorders.

Based on generally accepted approaches, the drug should be used with caution in elderly patients. This is especially true in frail or low-weight elderly people; they are recommended to prescribe the drug at the minimum effective dose.

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 ineffective.

Release form

3 ml of the drug in a glass ampoule . 5 ampoules in a blister of PVC film are packed in a cardboard box with instructions for medical use.

Food conditions

Store in a dry place, protected from light, at a temperature not exceeding 25ºС.

The drug should not be used after the expiration date.

Best before date

3 years.

Keep out of the reach of children.

Conditions for dispensing from pharmacies

On prescription.

Manufacturer

Ankur Drugs and Pharma Limited, Unit-II

Village-Makhnumajra, PO Bhud,

Distt-Solan (H.P.) 173205, India.

Name and address of the organization accepting claims (suggestions) regarding the quality of medicines in the territory of the Republic of Uzbekistan:

«SHAYANA FARM» LLC , ul. Usta Shirin, house-117, g. Tashkent — 700057, Republic of Uzbekistan.

Tel.: 99 (871) 2281692 (93/94) Fax: 99 (871) 2281695

QUPEN

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QUPEN

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