Diclofenac

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

Composition:

Active substance: diclofenac sodium;

1 g of gel contains 50 mg of diclofenac sodium;

Excipients: tromethamine, macrogol 400, methylparaben (E 218), carbopol ultrez 21, ethanol 96%, glycerin, purified water.

Pharmaceutical form. Gel.

Main physicochemical properties: homogeneous white or almost white gel.

Pharmacotherapeutic group.

Agents used locally for joint and muscular pain. Topical non-steroidal anti-inflammatory drugs. Diclofenac. ATC code M02A A15.

Pharmacological Properties.

Pharmacodynamics.

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

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.

Pharmacokinetics.

Sodium diclofenac is slowly and partially absorbed through the skin surface. The amount of diclofenac absorbed through the skin 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, peak plasma concentration is reached approximately within 1–2 hours. The mean duration of retention 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, 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 exert its effect and is found at 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 in urine. Total systemic plasma clearance of diclofenac is 263 ± 56 ml/min, and the terminal half-life averages 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 excreted via 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, or to any component of the medicinal product. History of asthma attacks, urticaria, acute rhinitis, nasal polyps, angioedema induced by the use of acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs. Third trimester of pregnancy. Pediatric age.

Interaction with other medicinal products and other forms of interaction.

Since systemic absorption of diclofenac following topical application of the drug 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 agents.

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

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

If any skin rash occurs, treatment with diclofenac should be discontinued. Application under an airtight occlusive dressing is not recommended; however, use under a non-occlusive dressing is permitted. In cases 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.

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

Pregnancy. There are no clinical data on the use of diclofenac during pregnancy. Even though systemic exposure is lower than with oral administration, it is unknown whether the systemic exposure to diclofenac achieved after topical application could be harmful to the embryo/fetus. During the first and second trimesters of pregnancy, diclofenac should not be used 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 cardiovascular and renal toxicity in the fetus, impairment of fetal kidney function leading to oligohydramnios, and/or development of cardiovascular and pulmonary toxicity, including premature closure of the ductus arteriosus and pulmonary hypertension. Impaired fetal renal function with subsequent oligohydramnios has been observed following use of NSAIDs (including diclofenac) from the 20th week of pregnancy.

At late stages of pregnancy, prolonged bleeding may occur in both mother and child, and labor may be delayed. Therefore, diclofenac is contraindicated during the last trimester of pregnancy (see section "Contraindications").

It is unknown whether diclofenac penetrates into breast milk following topical application. Therefore, the use of diclofenac 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 breasts or large skin areas and should not be used in larger amounts or for longer 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

Diclofenac should be applied 3–4 times daily, gently rubbed into the skin. The amount of the drug used depends on the size of the affected area (for example, 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 unless 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.

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

Geriatric patients (aged 65 years and older)

There are no grounds to believe that geriatric patients require a specific dose adjustment or are at increased risk of adverse reactions compared to other patients.

Patients with renal impairment

There are no grounds to believe that patients with renal impairment require a specific dose adjustment.

Patients with hepatic impairment

There are no grounds to believe that patients with hepatic impairment require a specific dose adjustment.

Children

Dosage recommendations and therapeutic indications for the use of Diclofenac in children are not established.

Overdose

Overdose is unlikely due to the low systemic absorption of diclofenac following topical application. However, in case of accidental ingestion, it should be noted that one 100 g tube contains the equivalent of 1 g of sodium diclofenac; systemic adverse reactions may therefore occur.

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

Adverse Reactions

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

The assessment of adverse reactions is listed according to frequency of occurrence: 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: rare – pustular eruptions.

Skin and subcutaneous tissue disorders: uncommon – rash, pruritus, erythema, eczema, exanthema, erythema, burning sensation, edema, vesicles, papules, pustules, desquamation, dry skin, 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 to large areas of skin, the possibility of systemic adverse reactions cannot be excluded, as well as hypersensitivity reactions such as angioedema and dyspnea.

Reporting of adverse reactions after drug registration is of great importance. This enables continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua.

Shelf life. 3 years.

Storage conditions.

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

Keep out of reach and sight of children.

Packaging.

40 g, 50 g, or 100 g of gel in a tube, in a carton or without a carton.

Prescription status.

Over-the-counter.

Manufacturer.

JSC "Pharmaceutical Factory "Viola".

Manufacturer's address and place of business.

75 Amosova Akademika Street, Zaporizhzhia, Ukraine, 69063.