Clodifen

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

Composition:

Active substance: diclofenac;

1 g of gel contains sodium diclofenac 10 mg;

Excipients: carbomer 980, propylene glycol, triethanolamine, ethanol 96%, methyl parahydroxybenzoate (E 218), purified water.

Pharmaceutical form. Gel.

Main physicochemical properties: transparent, colorless to slightly yellowish homogeneous gel, free from bubbles, with a faint alcoholic odor.

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 nonsteroidal anti-inflammatory drug (NSAID) with pronounced anti-rheumatic, analgesic, anti-inflammatory, and antipyretic effects. Its primary mechanism of action is the inhibition of prostaglandin biosynthesis.

In inflammation caused by injuries or rheumatic diseases, the drug reduces pain, tissue swelling, and shortens the recovery period of functions in damaged joints, ligaments, tendons, and muscles. Acute pain is reduced within 1 hour after the initial application. The majority of patients respond within 2 days of treatment. Relief from pain and functional impairments is achieved after 4 days of treatment with the drug. Due to its aqueous-alcoholic base, the preparation also provides local anesthetic and cooling effects.

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 to a skin surface area of 500 cm², the extent of 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 the wrist 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. Protein binding of diclofenac is 99.7%.

Diclofenac accumulates in the skin, which acts as a reservoir, allowing gradual release of the substance into adjacent tissues. From there, diclofenac primarily penetrates into deeper inflamed tissues, such as joints, where it continues to exert its action and is found in concentrations up to 20 times higher than in blood plasma.

Diclofenac is predominantly metabolized via hydroxylation, forming several phenolic derivatives, two of which are pharmacologically active, although significantly less so than diclofenac.

Diclofenac and its metabolites are primarily excreted in urine. The total systemic plasma clearance of diclofenac is 263±56 mL/min, and the terminal half-life is on average 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 or to any of the excipients.
• History of asthma attacks, angioedema, urticaria, or acute rhinitis induced by acetylsalicylic acid or other NSAIDs.
• Third trimester of pregnancy.

Interaction with other medicinal products and other forms of interaction.

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

Special precautions for use.

The drug should be used with caution in combination with oral NSAIDs due to the potential for enhanced adverse effects, including systemic side effects. The drug should not be used concurrently with other products containing diclofenac.

The possibility of systemic adverse reactions (which occur during systemic administration of diclofenac) should be considered when the drug is applied to larger skin areas or for longer durations than recommended. In such cases, the drug should be used cautiously in patients with hepatic, renal, or cardiac insufficiency, as well as in those with active peptic ulcer disease.

If any skin rash develops, the use of the drug should be discontinued.

The drug should be applied only to intact skin areas, avoiding application to inflamed, injured, or infected skin. Contact of the drug with eyes and mucous membranes should be avoided. The drug must not be swallowed.

The drug should not be used under airtight occlusive dressings; however, its use under non-occlusive dressings is permitted. In case of ligament strain, the affected area may be bandaged with a bandage.

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 therapy.

In isolated cases, gastrointestinal bleeding has been reported in patients with a long history of gastrointestinal disorders.

The drug contains propylene glycol, which may cause skin irritation, and methylparahydroxybenzoate (E 218), which may cause allergic reactions (possibly delayed).

Use during pregnancy or breastfeeding.

Clinical experience with use in pregnant women is limited. Systemic effects of diclofenac following topical application are lower than those observed with oral administration. It is unknown whether systemic exposure to topically applied diclofenac may be harmful to the embryo/fetus. Like other NSAIDs, the drug is contraindicated during the third trimester of pregnancy (see section "Contraindications") due to the risk of impaired labor, fetal renal dysfunction leading to oligohydramnios, and/or cardiopulmonary toxicity, including premature closure of the ductus arteriosus and pulmonary hypertension.

At late stages of pregnancy, prolonged bleeding may occur in both mother and child, and labor may be delayed.

Use of the drug during the first two trimesters of pregnancy is permitted only if the expected benefit outweighs the potential risk to the fetus. Women who are planning pregnancy or are in the first two trimesters of pregnancy should use the lowest possible dose and limit the duration of treatment.

It is unknown whether diclofenac is excreted in breast milk following topical application; therefore, use of the drug during breastfeeding is permitted only if the expected benefit outweighs the potential risk to the infant. If there are strong medical reasons for using the drug during breastfeeding, it should not be applied to the breasts or large skin areas, nor should it be used in higher amounts or for longer durations than recommended.

There are no 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

Adults and children aged 14 years and older

The medication is intended for topical application.

Apply the gel to the affected area of the skin 3–4 times daily, gently rubbing it into the skin. The amount used depends on the size of the affected area (2–4 g, corresponding in size to 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 area being treated is the hands themselves.

The duration of treatment depends on the nature of the condition and the response to therapy. The medication should not be used for longer than 14 consecutive days for injuries or soft tissue rheumatism, or for longer than 21 days for arthritic joint pain, unless otherwise directed by a physician.

If symptoms do not improve or worsen after 7 days of treatment, consult a physician.

Elderly patients

Elderly patients do not require dose adjustment.

Children

The medication is not recommended for children under 14 years of age. If used in children aged 14 years and older for longer than 7 days, or if symptoms worsen, medical advice should be sought.

Overdose

Overdose is unlikely due to the low systemic absorption of diclofenac following topical application. However, in case of accidental ingestion, note that one 45 g tube of the medication contains the equivalent of 450 mg of sodium diclofenac, which may lead to systemic adverse reactions.

In case of accidental ingestion, the stomach should be emptied immediately and an adsorbent administered. Symptomatic treatment is indicated, using therapeutic measures appropriate for NSAID poisoning.

Side effects

Side effects are classified according to frequency: very common: (>1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10,000, <1/1000); very rare (<1/10,000); frequency not known (cannot be estimated from the available data).

Infections and infestations:

very rare – pustular eruptions.

Immune system disorders:

very rare – hypersensitivity reactions (including urticaria), angioneurotic edema.

Respiratory, thoracic and mediastinal disorders:

very rare – bronchial asthma.

Skin and subcutaneous tissue disorders:

common – rash, eczema, erythema, dermatitis (including contact dermatitis), pruritus; rare – bullous dermatitis; very rare – photosensitivity reactions, skin burning sensation.

Although less likely with topical use, some side effects associated with systemic diclofenac administration may still occur.

If side effects occur, treatment should be discontinued and medical advice should be sought.

Reporting of suspected side effects.

Reporting of suspected adverse reactions occurring after marketing authorization is highly important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are requested to report any suspected adverse reactions via the national reporting system.

Shelf life.

3 years.

Storage conditions.

Store at temperatures not exceeding 25 °C, in a place inaccessible to children.

Packaging.

Gel, 45 g in aluminum tubes. One tube per cardboard box.

Supply classification.

Over-the-counter (without prescription).

Manufacturer.

K.O. SLAVIA PHARM S.R.L.
S.C. SLAVIA PHARM S.R.L.

Manufacturer's address and place of business.

Boulevard Theodor Pallady № 44 C, sector 3, 032266, Bucharest, Romania.

Marketing authorization holder.

WORLD MEDICINE, LLC, Ukraine.