Dicloberl Retard prolonged-release hard capsules 100 mg, 20 pcs

Pharmacological Properties

Pharmacodynamics

Diclofenac, the active substance of Dicloberl, is a non-steroidal compound with pronounced antirheumatic, antipyretic, analgesic, and anti-inflammatory properties. The main mechanism of action of diclofenac, established experimentally, is considered to be the inhibition of prostaglandin biosynthesis. Prostaglandins play an important role in the genesis of inflammation, pain, and fever.

In vitro, diclofenac sodium at concentrations equivalent to those achieved during patient treatment does not inhibit the biosynthesis of proteoglycans in cartilage tissue.

In rheumatic diseases, the anti-inflammatory and analgesic effects of Dicloberl contribute to a significant reduction in pain intensity (both at rest and during movement), morning stiffness, and joint swelling, thereby improving the patient’s functional condition.

In cases of inflammation caused by trauma or surgical intervention, Dicloberl rapidly eliminates both spontaneous pain and pain on movement, as well as reduces inflammatory tissue swelling and swelling in the area of the surgical wound. When used concomitantly with opioids to relieve postoperative pain, Dicloberl significantly reduces the need for opioids.

Clinical studies have demonstrated that diclofenac also exhibits a strong analgesic effect in moderate to severe pain of non-rheumatic origin.

Pharmacokinetics

Analysis of unchanged diclofenac and its hydroxylated metabolites excreted in urine showed that the amount of released and absorbed diclofenac is the same as when using an equivalent dose of diclofenac sodium in enteric-coated tablet form. However, the systemic bioavailability of diclofenac released from Dicloberl Retard averages about 82% of that observed after oral administration of enteric-coated Dicloberl tablets at the same dose.

Due to the slow release of the active substance from Dicloberl Retard, maximum plasma concentrations are lower than after the use of enteric-coated tablets. Mean peak concentrations of 0.4 or 0.5 μg/ml (1.25 or 1.6 μmol/l) are reached on average 5–6 hours after administration of a 75 mg or 100 mg tablet. Mean peak plasma concentrations of 1.48 ± 0.65 μg/ml are reached on average 2 hours after administration of a 50 mg tablet.

Food intake does not clinically affect the absorption or systemic bioavailability of Dicloberl. Mean plasma concentrations of 13 ng/ml may be observed 24 hours after administration of prolonged-release diclofenac sodium 75 mg. The amount of absorbed active substance is linearly dependent on the dose.

Approximately half of diclofenac is metabolized during first-pass hepatic metabolism. Therefore, the area under the curve after oral administration of Dicloberl Retard capsules is almost half that observed after parenteral administration of an equivalent dose. After repeated administration, pharmacokinetic parameters do not change, and no accumulation is observed when recommended dosing intervals are followed.

Distribution

Diclofenac is 99.7% bound to serum proteins, mainly albumin (99.4%). The volume of distribution is 0.12–0.17 l/kg. Diclofenac penetrates into synovial fluid, where maximum concentrations are observed 2–4 hours later than in plasma. The apparent half-life from synovial fluid is 3–6 hours.

Biotransformation

Diclofenac is metabolized partly by glucuronidation of the unchanged molecule and mainly by single and multiple hydroxylation and methoxylation, resulting in several phenolic metabolites. Two of these metabolites are pharmacologically active but to a much lesser extent than diclofenac.

Elimination

Total systemic clearance of diclofenac from plasma is 263 ± 56 ml/min. The terminal plasma half-life is 1–2 hours. About 60% of the administered dose is excreted in urine as conjugates of the intact active substance and metabolites. Less than 1% is excreted unchanged. The remainder is excreted as metabolites via bile in feces.

Indications

Relief of pain and reduction of inflammation of varying intensity in conditions including joint disorders such as rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, acute gout attacks; acute musculoskeletal conditions such as periarthritis, tendinitis, tenosynovitis, bursitis; and other conditions caused by trauma, including fractures, low back pain, sprains, dislocations, orthopedic and dental procedures, and other minor surgical interventions.

Dosage and Administration

The dose should be selected individually, starting with the lowest effective dose and used for the shortest possible duration.

The recommended initial dose for adults is 75–150 mg per day, depending on symptom severity. For long-term therapy, 100 mg once daily is usually sufficient. If symptoms are more pronounced at night or in the morning, the product should be taken in the evening. The daily dose should not exceed 150 mg.

Capsules should be swallowed whole, without chewing, with liquid, preferably during meals.

Contraindications

Hypersensitivity to diclofenac or any component of the product; active gastric or intestinal ulcer; gastrointestinal bleeding or perforation; severe hepatic, renal, or cardiac failure; third trimester of pregnancy; inflammatory bowel disease; history of NSAID-related gastrointestinal bleeding; and other conditions listed for non-steroidal anti-inflammatory drugs.

Side Effects

Possible adverse reactions include disorders of the blood and lymphatic system, immune system reactions, psychiatric disorders, nervous system disorders, visual disturbances, hearing disorders, cardiovascular events, respiratory reactions, gastrointestinal disturbances, hepatic reactions, skin and subcutaneous tissue reactions, renal disorders, and general disorders such as edema.

Special Warnings and Precautions

Treatment should begin with the lowest effective dose. Concomitant use with other systemic NSAIDs should be avoided. Elderly patients require particular caution due to an increased risk of adverse reactions.

Use During Pregnancy and Breastfeeding

During the first and second trimesters of pregnancy, diclofenac should only be used if clearly necessary. Use is contraindicated during the third trimester. Diclofenac should not be used during breastfeeding.

Ability to Drive and Use Machines

Patients experiencing dizziness, visual disturbances, drowsiness, or other central nervous system effects should avoid driving vehicles or operating machinery.

Interactions

Diclofenac may interact with lithium, digoxin, diuretics, antihypertensive agents, anticoagulants, antiplatelet agents, other NSAIDs, corticosteroids, antidepressants, antidiabetic agents, methotrexate, cyclosporine, tacrolimus, quinolones, phenytoin, and other medicinal products.

Overdose

Symptoms may include headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, dizziness, drowsiness, and seizures. Treatment is symptomatic and supportive.

Storage Conditions

Tablets: store at a temperature not exceeding 30°C. Capsules: store at a temperature not exceeding 25°C.