Diclofenac sodium

INSTRUCTIONS FOR MEDICAL USE OF MEDICINAL PRODUCT

DICLOFENAC SODIUM (DICLOFENAC SODIUM)

Composition:

Active substance: diclofenac;

1 g of gel contains 50 mg of sodium diclofenac;

Excipients: isopropyl alcohol, purified water, macrogol-7-glycerol cocoate, hypromellose.

Pharmaceutical form. Gel.

Main physico-chemical properties: colorless or slightly yellowish transparent gel with a characteristic odor of isopropanol, free from air bubbles.

Pharmacotherapeutic group. Agents used locally for joint and muscular pain. Topically applied non-steroidal anti-inflammatory drugs. Diclofenac.

ATC code M02A A15.

Pharmacological Properties.

Pharmacodynamics.

The gel is a non-steroidal anti-inflammatory agent for topical use, belonging to the phenylacetic acid derivatives group. The drug exerts pronounced local anti-rheumatic, analgesic, and anti-inflammatory effects, which are due to inhibition of prostaglandin synthesis—the mediators of pain and inflammation.

In inflammation caused by injuries or rheumatic diseases, the gel reduces pain, tissue swelling, and shortens the recovery period of functions in damaged joints, ligaments, tendons, and muscles.

Pharmacokinetics.

Sodium diclofenac is slowly and partially absorbed through the skin surface. The amount of diclofenac absorbed is proportional to the application area and depends on both the total applied dose of the drug and the degree of skin hydration. Maximum plasma concentration is observed within 6–9 hours. After oral administration, maximum plasma concentration is reached approximately within 1–2 hours. The mean duration of the active substance in systemic circulation is about 9 hours, which is significantly longer compared to 1–2 hours after oral administration.

Diclofenac accumulates in the skin, which acts as a reservoir, allowing gradual release of the substance 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 plasma.

Metabolism and elimination of the drug after topical application are similar to those following systemic administration. Diclofenac and its metabolites are primarily excreted via urine. Total systemic plasma clearance of diclofenac is 263 + 56 ml/min, and the mean terminal half-life is 1–3 hours. Diclofenac is 99% bound to plasma proteins. Following rapid hepatic metabolism (hydroxylation and conjugation with glucuronic acid), approximately two-thirds of the substance is eliminated by the kidneys and one-third via bile.

In renal or hepatic insufficiency, metabolism and elimination of diclofenac from the body remain unchanged.

Clinical characteristics.

Indications.

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

Contraindications.

Hypersensitivity to diclofenac or to other nonsteroidal anti-inflammatory drugs, to isopropyl alcohol or to any of the excipients of the medicinal product. History of asthma attacks, urticaria, acute rhinitis, nasal polyps, or angioedema induced by administration of acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs. Third trimester of pregnancy. Childhood.

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 occurrence of interactions is unlikely.

Special precautions for use.

The drug should be used with caution in combination with oral nonsteroidal anti-inflammatory drugs.

The likelihood of developing systemic adverse effects with topical application of dicloenac is low compared to oral formulations; however, it cannot be excluded when the drug is applied over relatively large skin areas for prolonged periods.

The gel should only be applied to intact skin areas, avoiding contact with inflamed, damaged, or infected skin. Contact of the drug with eyes and mucous membranes should be avoided. The drug must not be used internally.

If any skin rash occurs, treatment with the drug should be discontinued. Use under an occlusive airtight dressing is not recommended; however, application under a non-occlusive dressing is permitted. In case of ligament sprains, the affected area may be bandaged.

Do not apply to open wounds or infected skin, or to skin areas affected by eczema, or to mucous membranes.

The gel contains isopropyl alcohol, which may cause mild localized skin irritation.

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

Use during pregnancy or breastfeeding.

There are no clinical data on the use of the medicinal product during pregnancy. Even though systemic effects are 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 Sodium, may cause cardiopulmonary and renal toxicity in the fetus. In late 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").

Risk of impaired fetal renal function leading to oligohydramnios has been observed with the use of NSAIDs (including diclofenac) from the 20th week of pregnancy.

It is unknown whether diclofenac penetrates into breast milk following topical application; therefore, use of the medicinal product during breastfeeding is permitted only if the expected benefit outweighs the potential risk to the infant, as judged by the physician. If there are strong reasons for using the drug during breastfeeding, the gel should not be applied to the mammary glands or large skin areas, and should not be used in higher amounts or for longer durations than recommended.

Fertility. There are no available data on the effect of topically applied diclofenac on human fertility.

Ability to affect reaction speed when driving or operating machinery.

No effect.

Method of Administration and Dosage

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

After application, hands should be washed unless the hands themselves are the area being treated.

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

Do not use the drug for longer than 14 consecutive days.

If the drug is used without medical prescription, consult a physician if the patient's condition does not improve or worsens after 7 days of treatment.

Elderly patients (aged 65 years and older). There is no reason to believe that elderly patients require a special dose adjustment or are at increased risk of adverse reactions compared to other patients.

Patients with renal impairment. There is no reason to believe that patients with renal impairment require a special dose adjustment.

Patients with hepatic impairment. There is no reason to believe that patients with hepatic impairment require a special dose adjustment.

Children.

Dosage recommendations and therapeutic indications for use of the medicinal product in children are not available.

Overdose.

Overdose is unlikely due to the low systemic absorption of diclofenac when applied topically. In case of accidental ingestion, note that one 100-g tube of the product contains the equivalent of 1 g of sodium diclofenac, which may lead to systemic adverse reactions.

In case of accidental ingestion, gastric lavage should be performed immediately and an adsorbent administered. Symptomatic treatment using therapeutic measures appropriate for poisoning with nonsteroidal anti-inflammatory drugs is indicated.

Adverse Reactions

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

Adverse reactions are listed below by frequency: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1,000, < 1/100), rare (≥ 1/10,000, < 1/1,000), very rare (< 1/10,000).

Infections and infestations: very rare – pustular eruptions.

Skin disorders: uncommon – rash, pruritus, erythema, eczema, exanthema, erythema, burning sensation, edema and vesicle formation, papules, pustules, skin desquamation and dryness, dermatitis (including contact dermatitis); rare – bullous dermatitis; very rare – photosensitivity reactions, generalized skin eruptions, skin burning sensation.

Immune system disorders: very rare – hypersensitivity reactions (including urticaria), facial angioedema, dyspnea.

Respiratory system disorders: very rare – bronchial asthma.

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

When the gel is used in high doses or applied over large areas of skin, systemic adverse reactions as well as hypersensitivity reactions such as angioedema and dyspnea cannot be excluded.

Reporting of suspected adverse reactions after drug registration is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, and their legal representatives should report all suspected adverse reactions and lack of efficacy through the automated pharmacovigilance information system at: https://aisf.dec.gov.ua.

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.

50 g of gel in a tube № 1; in a cardboard box.

100 g of gel in a tube № 1; in a cardboard box.

Supply category. Over-the-counter.

Manufacturer.

JSC "CHEMICAL PHARMACEUTICAL PLANT "CHERVONA ZIRKA".

Manufacturer's address and place of business.

1, Gordienkovska Street, Kharkiv, Kharkiv Oblast, 61010, Ukraine.