Diclofenac

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DICLOFENAC (DICLOFENAC)

Composition:

Active substance: diclofenac;

1 g of gel contains: sodium diclofenac – 50 mg;

Excipients: ethanol 96%, glycerin, mineral oil, carbomer, hydrogenated polyethoxylated castor oil, methylparahydroxybenzoate (E 218), propylparahydroxybenzoate (E 216), ammonia solution 15%, propylene glycol, purified water.

Pharmaceutical form. Gel.

Main physicochemical properties: white or off-white homogeneous gel.

Pharmacotherapeutic group.

Agents used locally for joint and muscular pain. Topical non-steroidal anti-inflammatory agents. Diclofenac.

ATC code M02A A15.

Pharmacological properties.

Pharmacodynamics.

Diclofenac is a non-steroidal anti-inflammatory agent with pronounced anti-rheumatic, analgesic, anti-inflammatory, and antipyretic effects. Its main mechanism of action is the inhibition of prostaglandin biosynthesis.

In inflammation caused by injuries or rheumatic diseases, Diclofenac reduces pain, tissue swelling, and shortens the recovery period of functions in damaged joints, ligaments, tendons, and muscles. Diclofenac reduces acute pain within 1 hour after the initial application. Relief of pain and functional impairments is achieved after 4 days of treatment with Diclofenac. Due to its water-alcohol base, the preparation also exerts a local anesthetic and cooling effect.

Pharmacokinetics.

The amount of diclofenac absorbed through the skin is proportional to the application area and depends on both the total dose applied and the degree of skin hydration. After topical application of 2.5 g of Diclofenac preparation to a skin surface area of 500 cm², the extent of diclofenac absorption is approximately 6%. Application of an occlusive dressing for 10 hours results in a threefold increase in diclofenac absorption.

After application of Diclofenac to the skin over hand and knee joints, diclofenac is detected in blood plasma (where its maximum concentration is approximately 100 times lower than after oral administration), in the synovial membrane, and in synovial fluid. Diclofenac protein binding is 99.7%.

Diclofenac accumulates in the skin, which acts as a reservoir from which the substance is gradually released into adjacent tissues. From there, diclofenac predominantly penetrates into deeper inflamed tissues, such as joints, where it continues to act and is found in concentrations up to 20 times higher than in blood plasma.

Diclofenac is metabolized primarily via hydroxylation, forming several phenolic derivatives, two of which are pharmacologically active, although to a much lesser extent than diclofenac.

Diclofenac and its metabolites are excreted predominantly in urine. The total systemic plasma clearance of diclofenac is 263 ± 56 ml/min, and the terminal half-life averages 1–3 hours.

In renal or hepatic insufficiency, the metabolism and elimination of diclofenac are not altered.

Clinical characteristics.

Indications.

Local treatment of pain and inflammation of joints, muscles, ligaments, and tendons of rheumatic or traumatic origin.

Contraindications.

Hypersensitivity to diclofenac, other nonsteroidal anti-inflammatory drugs (NSAIDs), or to any component of the medicinal product. History of asthma attacks, angioedema, urticaria, or acute rhinitis induced by acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs. Third trimester of pregnancy.

Interaction with other medicinal products and other forms of interaction.

Since systemic absorption of diclofenac following topical application of the product is very low, the likelihood of interactions is very low.

Special precautions for use.

Use with caution when administered concomitantly with oral nonsteroidal anti-inflammatory drugs.

The likelihood of developing systemic adverse effects with topical application of diclofenac is low compared to oral formulations; however, this risk increases when the drug is applied over relatively large skin areas for prolonged periods. In such cases, the medicinal product should be used with caution in patients with hepatic, renal, or cardiac insufficiency, as well as in those with active peptic ulcer disease.

Diclofenac should be applied only to intact skin areas, avoiding contact with inflamed, injured, or infected skin, as well as skin areas affected by eczema. Contact of the product with eyes and mucous membranes should be avoided. The gel must not be swallowed.

If any skin rash develops, treatment with the drug should be discontinued. Diclofenac should not be used under airtight occlusive dressings; however, application under non-occlusive dressings is acceptable. In cases of ligament sprains, the affected area may be bandaged with a compression bandage.

Cases of gastrointestinal bleeding have been reported in individual patients with a history of chronic gastrointestinal disorders.

The medicinal product contains: propylene glycol, which may cause mild localized skin irritation; hydrogenated polyethoxylated castor oil, which may cause skin reactions; methylparahydroxybenzoate (E 218) and propylparahydroxybenzoate (E 216), which may cause allergic reactions (possibly delayed).

Due to the possibility of photosensitivity reactions, exposure to direct sunlight and visits to solariums should be avoided during treatment and for 2 weeks after discontinuation of therapy.

Use during pregnancy or breastfeeding.

There are no clinical data on the use of the medicinal product during pregnancy. Even though systemic exposure is lower than with oral administration, it is unknown whether the systemic exposure achieved after topical application could be harmful to the embryo/fetus. The medicinal product should not be used during the first and second trimesters of pregnancy unless clearly necessary. If used, the dose should be as low as possible and the duration of treatment as short as possible.

During the third trimester of pregnancy, systemic use of prostaglandin synthesis inhibitors, including diclofenac, may cause cardiopulmonary and renal toxicity in the fetus. At late stages of pregnancy, prolonged bleeding may occur in both mother and child, and labor may be delayed. Therefore, the medicinal product is contraindicated during the third trimester of pregnancy (see section "Contraindications").

It is unknown whether diclofenac is excreted in breast milk following topical application. Therefore, use of diclofenac during breastfeeding is permitted only if the expected benefit outweighs the potential risk to the infant. In such cases, the drug should not be applied to the breasts or large areas of skin, and should not be used in higher amounts or for longer than recommended.

Data on the effect of diclofenac on human fertility following topical application are lacking.

Ability to affect reaction speed when driving or operating machinery.

No effect.

Dosage and Administration

Apply diclofenac 3–4 times daily, gently rubbing it into the skin. The amount used depends on the size of the affected area (2–4 g of gel, corresponding in size to a cherry or a walnut, is sufficient for application to an area of 400–800 cm²).

After application, hands should be washed, except when the hands themselves are the treated area.

The duration of therapy depends on the nature of the disease and the treatment response.

The drug should not be used for longer than 14 consecutive days.

Children

Dosage recommendations and therapeutic indications for use in children are not available.

Overdose

Overdose is unlikely due to low systemic absorption of diclofenac following topical application. In case of accidental ingestion, note that one 40-g tube contains the equivalent of 2 g of sodium diclofenac, which may lead to the development of systemic adverse reactions.

In the event of accidental ingestion, the stomach should be emptied immediately and an adsorbent administered. Symptomatic treatment should be implemented, using therapeutic measures appropriate for poisoning with nonsteroidal anti-inflammatory drugs.

Adverse reactions.

Diclofenac is generally well tolerated. Adverse reactions include mild transient skin reactions at the application site. Allergic reactions may occur rarely.

Adverse reactions are classified according to frequency: very common (>1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10000, <1/1000); very rare (<1/10000); frequency not known (cannot be estimated from available data).

Infections and infestations

very rare – pustular rashes.

Immune system disorders

very rare – hypersensitivity reactions (including urticaria), angioedema, dyspnea.

Respiratory system disorders

very rare – bronchial asthma.

Skin and connective tissue disorders

common – rash, erythema, eczema, exanthema, erythema, dermatitis including contact dermatitis, pruritus, burning sensation, swelling and vesicle formation, papules, pustules, desquamation and dryness of the skin; rare – bullous dermatitis;

very rare – photosensitivity reactions, skin burning sensation, generalized skin rashes.

Gastrointestinal disorders adverse reactions occur very rarely after topical application of preparations containing diclofenac.

When applying the gel in high doses or over large areas of skin, the possibility of systemic adverse reactions cannot be excluded, as well as hypersensitivity reactions manifesting as angioedema, dyspnea.

If adverse reactions occur, treatment should be discontinued and medical advice should be sought.

Shelf life. 2 years.

Do not use after the expiry date stated on the packaging.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

40 g of gel in an aluminum tube No. 1; in a cardboard pack.

100 g in a laminated tube No. 1; in a cardboard pack.

Prescription status.

Over-the-counter.

Manufacturer.

JSC "CHEMICAL PHARMACEUTICAL PLANT "CHERVONA ZIRKA".

Manufacturer's address and location of business activity.

1, Hordienkivska Street, Kharkiv, Kharkiv region, 61010, Ukraine.