Diclofenak Stada^® (Tablets, Capsules, Suppositories) Instructions for Use

ATC Code

M01AB05 (Diclofenac)

Active Substance

Diclofenac (Rec.INN registered by WHO)

Clinical-Pharmacological Group

NSAID

Pharmacotherapeutic Group

NSAID

Pharmacological Action

NSAID, a derivative of phenylacetic acid. It has a pronounced anti-inflammatory, analgesic, and moderate antipyretic effect.

The mechanism of action is associated with the inhibition of COX activity, the main enzyme in the metabolism of arachidonic acid, which is a precursor of prostaglandins that play an important role in the pathogenesis of inflammation, pain, and fever.

The analgesic effect is due to two mechanisms: peripheral (indirectly, through suppression of prostaglandin synthesis) and central (due to inhibition of prostaglandin synthesis in the central and peripheral nervous system).

In vitro, at concentrations equivalent to those achieved in the treatment of patients, it does not inhibit the biosynthesis of proteoglycans in cartilage tissue.

In rheumatic diseases, it reduces joint pain at rest and during movement, as well as morning stiffness and joint swelling, and helps increase the range of motion.

It reduces post-traumatic and postoperative pain, as well as inflammatory edema.

In post-traumatic and postoperative inflammatory phenomena, it quickly relieves pain (occurring both at rest and during movement), reduces inflammatory edema and postoperative wound edema.

It inhibits platelet aggregation. With long-term use, it has a desensitizing effect.

Pharmacokinetics

After oral administration, it is absorbed from the gastrointestinal tract. Food intake slows down the rate of absorption, but the extent of absorption does not change. About 50% of the active substance is metabolized during the first pass through the liver.

With rectal administration, absorption occurs more slowly than with oral and intramuscular administration. The time to reach C_max in plasma after rectal administration is 1 hour. The concentration of the active substance in the plasma is linearly dependent on the applied dose.

It does not accumulate. Binding to plasma proteins is 99.7% (mainly with albumin). It penetrates into the synovial fluid; C_max is reached 2-4 hours later than in plasma.

It is largely metabolized to form several metabolites, two of which are pharmacologically active, but to a lesser extent than Diclofenac.

The systemic clearance of the active substance is approximately 263 ml/min. T_1/2 from plasma is 1-2 hours, from synovial fluid – 3-6 hours. Approximately 60% of the dose is excreted by the kidneys as metabolites, less than 1% is excreted unchanged in the urine, the rest is excreted as metabolites with bile.

Indications

Inflammatory and degenerative diseases of the musculoskeletal system, including rheumatoid, juvenile, chronic arthritis; ankylosing spondylitis and other spondyloarthropathies; osteoarthritis; gouty arthritis; bursitis, tenosynovitis; pain syndrome from the spine (lumbago, sciatica, ossalgia, neuralgia, myalgia, arthralgia, radiculitis); post-traumatic postoperative pain syndrome accompanied by inflammation (for example, in dentistry and orthopedics); algodysmenorrhea; inflammatory processes in the pelvis (including adnexitis); infectious and inflammatory diseases of the ENT organs with severe pain syndrome (as part of complex therapy): pharyngitis, tonsillitis, otitis.

Isolated fever is not an indication for the use of the drug.

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

ICD codes

Dosage Regimen

Tablets, Capsules

The dose is selected individually; it is recommended to use the minimum effective dose, with the shortest possible treatment period.

Suppositories

The dose is selected individually; it is recommended to use the drug in the minimum effective dose, with the shortest possible treatment period.

For adults, the recommended initial dose is 100-150 mg/day. In relatively mild cases of the disease, as well as for long-term therapy, 75-100 mg/day may be sufficient.

When used in combination orally in the form of tablets and rectally in the form of suppositories, the total daily dose should not exceed 150 mg.

In debilitated patients, patients with low body weight, it is recommended to adhere to the minimum dose.

The drug should be used with particular caution in patients with cardiovascular diseases (including uncontrolled arterial hypertension) or a high risk of developing cardiovascular diseases. If long-term therapy (more than 4 weeks) is necessary in such patients, the drug should be used in a daily dose not exceeding 100 mg.

Children aged 1 year and older

The drug is prescribed at a dose of 0.5-2 mg/kg body weight/day (in 2-3 doses, depending on the severity of the disease). For the treatment of rheumatoid arthritis, the daily dose can be increased to a maximum of 3 mg/kg (in several doses). The maximum daily dose is 150 mg.

Adverse Reactions

From the digestive system: frequently – abdominal pain, nausea, vomiting, diarrhea, dyspepsia, flatulence, decreased appetite, anorexia, increased activity of aminotransferases in blood serum; rarely – gastritis, gastrointestinal bleeding, hematemesis, melena, diarrhea with blood, gastric and intestinal ulcers (with or without bleeding or perforation), hepatitis, jaundice, impaired liver function; very rarely – stomatitis, glossitis, esophageal lesions, occurrence of diaphragm-like strictures in the intestine, colitis (non-specific hemorrhagic colitis, exacerbation of ulcerative colitis or Crohn’s disease), constipation, pancreatitis, fulminant hepatitis, liver necrosis, liver failure.

From the nervous system: frequently – headache, dizziness; rarely – drowsiness; very rarely – sensitivity disorders, including paresthesia, memory disorders, tremor, convulsions, anxiety, acute cerebrovascular accidents, aseptic meningitis; very rarely – disorientation, depression, insomnia, nightmares, irritability, mental disorders.

From the sensory organs: frequently – vertigo; very rarely – visual disturbances (blurred vision), diplopia, hearing impairment, tinnitus, dysgeusia.

Dermatological reactions: frequently – skin rash; rarely – urticaria; very rarely – bullous eruptions, eczema, erythema, erythema multiforme, Stevens-Johnson syndrome, Lyell’s syndrome (toxic epidermal necrolysis), exfoliative dermatitis, itching, hair loss, photosensitivity reactions; purpura, Henoch-Schönlein purpura.

From the genitourinary system: very rarely – acute renal failure, hematuria, proteinuria, tubulointerstitial nephritis, nephrotic syndrome, papillary necrosis.

From the hematopoietic system: very rarely – thrombocytopenia, leukopenia, hemolytic anemia, aplastic anemia, agranulocytosis.

Allergic reactions: rarely – hypersensitivity, anaphylactic/anaphylactoid reactions, including decreased blood pressure and shock; very rarely – angioedema (including facial edema).

From the cardiovascular system: very rarely – palpitations, chest pain, increased blood pressure, vasculitis, heart failure, myocardial infarction. There is evidence of a slight increase in the risk of cardiovascular thrombotic complications (e.g., myocardial infarction), especially with long-term use of diclofenac in high doses (daily dose more than 150 mg).

From the respiratory system: rarely – asthma (including shortness of breath); very rarely – pneumonitis.

General reactions: rarely – edema.

Contraindications

Hypersensitivity to diclofenac and excipients of the drug used; “aspirin triad” (attacks of bronchial asthma, urticaria and acute rhinitis when taking acetylsalicylic acid or other NSAIDs); erosive and ulcerative lesions of the gastrointestinal tract in the acute phase; proctitis; third trimester of pregnancy.

With caution

Suspected gastrointestinal disease; history of gastrointestinal bleeding and ulcer perforation (especially in elderly patients), Helicobacter pylori infection, ulcerative colitis, Crohn’s disease, liver function disorders; mild and moderate liver function disorders, hepatic porphyria (Diclofenac may provoke porphyria attacks); in patients with bronchial asthma, seasonal allergic rhinitis, edema of the nasal mucosa (including nasal polyps), COPD, chronic infectious diseases of the respiratory tract (especially those associated with allergic rhinitis-like symptoms); cardiovascular diseases (including coronary artery disease, cerebrovascular disease, compensated heart failure, peripheral vascular diseases); renal function disorders, including chronic renal failure (creatinine clearance 30-60 ml/min); dyslipidemia/hyperlipidemia; diabetes mellitus; arterial hypertension; significant decrease in circulating blood volume of any etiology (e.g., in the periods before and after major surgical interventions); hemostasis system disorders; risk of thrombosis (including myocardial infarction and stroke); elderly patients, especially debilitated or with low body weight (Diclofenac should be used in the minimum effective dose); in patients receiving drugs that increase the risk of gastrointestinal bleeding, including systemic glucocorticosteroids (including prednisolone), anticoagulants (including warfarin), antiplatelet agents (including clopidogrel, acetylsalicylic acid), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline); simultaneous treatment with diuretics or other drugs that can impair renal function; when treating smoking patients or patients who abuse alcohol; with intramuscular administration in patients with bronchial asthma due to the risk of exacerbation of the disease (since sodium bisulfite, which is contained in some injectable forms, can cause severe hypersensitivity reactions).

Use in Pregnancy and Lactation

There is insufficient data on the safety of diclofenac use in pregnant women. Therefore, prescription in the first and second trimesters of pregnancy is possible only in cases where the expected benefit to the mother outweighs the potential risk to the fetus.

Diclofenac (like other inhibitors of prostaglandin synthesis) is contraindicated in the third trimester of pregnancy (possible suppression of uterine contractility and premature closure of the fetal arterial duct).

Although Diclofenac is excreted in breast milk in small amounts, its use during breastfeeding is not recommended. If use during lactation is necessary, breastfeeding should be discontinued.

Since Diclofenac (like other NSAIDs) may have a negative effect on fertility, its use is not recommended in women planning pregnancy.

The drug should be discontinued in patients undergoing examination and treatment for infertility.

Use in Hepatic Impairment

Use with particular caution in patients with a history of liver disease.

Use in Renal Impairment

Use with particular caution in patients with a history of kidney disease.

Pediatric Use

Not recommended for use in children under 6 years of age.

Geriatric Use

Use with particular caution in elderly patients.

Special Precautions

Use with particular caution in patients with a history of liver, kidney, gastrointestinal diseases, dyspeptic symptoms, bronchial asthma, arterial hypertension, heart failure, immediately after major surgical interventions, as well as in elderly patients.

In case of a history of allergic reactions to NSAIDs and sulfites, Diclofenac should be used only in emergency cases. During treatment, systematic monitoring of liver and kidney function, peripheral blood picture is necessary.

Rectal use is not recommended in patients with anorectal diseases or a history of anorectal bleeding.

Avoid contact of diclofenac with the eyes or mucous membranes.

Not recommended for use in children under 6 years of age.

During treatment with systemic dosage forms, alcohol consumption is not recommended.

Effect on ability to drive vehicles and operate machinery

During treatment, a decrease in the speed of psychomotor reactions is possible. If visual clarity deteriorates after using eye drops, you should not drive a car or engage in other potentially hazardous activities.

Drug Interactions

Potent CYP2C9 inhibitors – when diclofenac and potent CYP2C9 inhibitors (such as voriconazole) are co-administered, an increase in the serum concentration of diclofenac and an enhancement of systemic effects due to inhibition of diclofenac metabolism are possible.

Lithium, digoxin – an increase in the plasma concentration of lithium and digoxin is possible. Monitoring of serum lithium and digoxin concentrations is recommended.

Diuretic and antihypertensive agents – when used concomitantly with diuretics and antihypertensive drugs (e.g., beta-blockers, ACE inhibitors), Diclofenac may reduce their antihypertensive effect.

Cyclosporine – the effect of diclofenac on prostaglandin activity in the kidneys may enhance the nephrotoxicity of cyclosporine.

Drugs that can cause hyperkalemia – concomitant use of diclofenac with potassium-sparing diuretics, cyclosporine, tacrolimus and trimethoprim may lead to an increase in plasma potassium levels (in case of such a combination, this indicator should be monitored frequently).

Antibacterial agents of the quinolone derivative – there are isolated reports of seizures in patients receiving quinolone derivatives and Diclofenac simultaneously.

NSAIDs and glucocorticosteroids – with simultaneous systemic use of diclofenac and other systemic NSAIDs or glucocorticosteroids, the frequency of adverse events (in particular, from the gastrointestinal tract) may increase.

Anticoagulants and antiplatelet agents – an increased risk of bleeding cannot be excluded when diclofenac is used concomitantly with drugs of these groups.

Selective serotonin reuptake inhibitors – an increased risk of gastrointestinal bleeding is possible.

Hypoglycemic drugs – cases of both hypoglycemia and hyperglycemia cannot be excluded, which necessitated a change in the dose of hypoglycemic drugs while using diclofenac.

Methotrexate – when diclofenac is used within 24 hours before or within 24 hours after methotrexate administration, an increase in the blood concentration of methotrexate and an enhancement of its toxic effect are possible.

Phenytoin – an enhancement of the effect of phenytoin is possible.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.