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: isopropyl alcohol, polyethylene glycol 400, hypromellose, citric acid monohydrate, purified water.

Pharmaceutical form. Gel.

Main physicochemical properties: colorless or slightly yellowish transparent gel of uniform consistency, with a characteristic odor of isopropyl alcohol.

Pharmacotherapeutic group.

Agents used locally for joint and muscular pain. Non-steroidal anti-inflammatory agents for topical use. Diclofenac.

ATC code M02A A15.

Pharmacological properties.

Pharmacodynamics.

Diclofenac is a topical nonsteroidal anti-inflammatory agent 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 helps reduce pain, tissue swelling, and shortens the recovery period of impaired functions of 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 both on the total applied dose of the drug and on 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 average duration of the active substance in systemic circulation is approximately 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 primarily enters deeper inflamed tissues, such as joints, where it continues to act and is found in concentrations nearly 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 mainly excreted via urine. Total systemic plasma clearance of diclofenac is 263 ± 56 mL/min, and the terminal half-life is on average 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 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.

For 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. History of asthma attacks, urticaria, acute rhinitis, nasal polyps, angioedema induced by 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 after topical application of the drug is very low, the occurrence of interactions is unlikely.

Special precautions for use.

Diclofenac should be used with caution in combination 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, systemic absorption is not excluded when the drug is applied over relatively large skin areas for prolonged periods.

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

Treatment should be discontinued if any skin rash develops. Use under an airtight occlusive dressing is not recommended; however, application 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.

The product 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 diclofenac 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. During the first and second trimesters of pregnancy, diclofenac should not be used unless clearly necessary. If use is required, 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. 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 topically applied diclofenac is excreted in breast milk. Therefore, the use of diclofenac during breastfeeding is permitted only if, in the physician’s opinion, the expected benefit outweighs the potential risk to the infant. If there are strong medical 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 durations than recommended.

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

Ability to influence reaction rate while driving or operating machinery.

No effect.

Dosage and Administration

Apply diclofenac 3–4 times daily, gently rubbing it into the skin. The amount of medication used depends on the size of the affected area (2–4 g of 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 applying the medication, hands should be washed unless the hands themselves are the area being treated.

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

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

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

Elderly patients (over 65 years of age). There is no evidence to suggest that elderly patients require a specific dose adjustment or are at increased risk of adverse reactions compared to other patients.

Patients with renal impairment. There is no evidence to suggest that patients with renal impairment require a specific dose adjustment.

Patients with hepatic impairment. There is no evidence to suggest 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 available.

Overdose.

Overdose is unlikely due to the low systemic absorption of diclofenac following topical application. However, in case of accidental ingestion, note that one 40 g tube of the medicinal product contains the equivalent of 2 g of sodium diclofenac, which may lead to systemic adverse effects.

In case of accidental ingestion, the stomach should be emptied immediately and an adsorbent administered. Symptomatic treatment is indicated, employing therapeutic measures commonly used in poisoning with nonsteroidal anti-inflammatory drugs.

Adverse reactions.

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

Assessment of adverse reactions by 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: very rare — pustular rashes.

Skin and subcutaneous tissue disorders: uncommon — rash, pruritus, erythema, eczema, exanthema, erythema, burning sensation, edema and vesicle formation, papules, pustules, desquamation and dryness of the skin, dermatitis (including contact dermatitis); rare — bullous dermatitis; very rare — photosensitivity reactions, generalized skin rashes, 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, systemic adverse reactions cannot be excluded, as well as hypersensitivity reactions such as angioedema and dyspnea.

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

Shelf life. 3 years.

Storage conditions.

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

Keep out of reach and sight of children.

Packaging.

35 g or 40 g in tubes; 35 g, 40 g or 100 g in tube, 1 tube in a cardboard box.

Supply category.

Over-the-counter.

Manufacturer.

JSC "Lubnipharm".

Manufacturer's address and location of business activity.

16, Barvinкова Street, Lubny, Poltava region, 37500, Ukraine.