Clodifen

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

Composition:

Active substance: diclofenac;

1 g of gel contains sodium diclofenac 50 mg;

Excipients: hydroxyethylcellulose, propylene glycol, ethanol 96%, methylparaben (E 218), purified water.

Pharmaceutical form. Gel.

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

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 drug (NSAID) for topical use, belonging to the phenylacetic acid derivatives group. It has pronounced local anti-rheumatic, analgesic, and anti-inflammatory properties, which are due to inhibition of prostaglandin synthesis—the mediators of pain and inflammation.

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.

Pharmacokinetics.

After topical application, 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 6–9 hours after topical application. After oral administration, peak plasma concentration is reached approximately within 1–2 hours. The average duration of active substance retention in systemic circulation is about 9 hours, which is significantly longer compared to 1–2 hours after oral administration. Protein binding of diclofenac is 99%.

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 exert its effect 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. After 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.

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 is on average 1–3 hours.

In renal or hepatic insufficiency, 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 NSAIDs, or to any of the excipients of the medicinal product.
• History of asthma attacks, urticaria, acute rhinitis, nasal polyps, or angioneurotic edema induced by acetylsalicylic acid or other NSAIDs.
• Last trimester of pregnancy.
• Age under 18 years.

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

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

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

If any skin rash occurs, administration of the drug should be discontinued.

The drug should be applied only to intact skin areas, avoiding contact with 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 air-impermeable occlusive dressings; however, its use under non-occlusive dressings is permitted. In case of ligament sprains, the affected area may be bandaged with a bandage.

Do not apply the drug 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 the drug.

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. As with other NSAIDs, the drug is contraindicated during the third trimester of pregnancy due to the risk of impaired uterine contractility, prolonged bleeding time, fetal renal dysfunction leading to oligohydramnios, and/or development of cardiopulmonary toxicity with premature closure of the ductus arteriosus and pulmonary hypertension. 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 planning pregnancy and those in the first two trimesters of pregnancy should use the lowest effective dose for the shortest duration possible.

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

It is unknown whether diclofenac is excreted in breast milk following topical application; therefore, use of the drug during breastfeeding should only be considered 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.

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

Ability to influence reaction rate while driving or operating machinery

No effect.

Method of administration and dosage.

Adults.

The medication is intended for topical use.

Apply the gel to the affected area of the skin 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, 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 hands themselves are the area being treated.

The duration of treatment depends on the nature of the disease and the treatment response. The medication should not be used for longer than 14 consecutive days. If symptoms do not improve or worsen after 7 days of treatment, consult a physician.

Elderly patients (over 65 years of age).

These patients do not require dose adjustment.

Patients with renal impairment.

There is no evidence to suggest that patients with renal impairment require special dose adjustment or are at increased risk of adverse reactions compared to other patients.

Patients with hepatic impairment.

There is no evidence to suggest that patients with hepatic impairment require special dose adjustment.

Children.

Dosage recommendations and therapeutic indications for use of the medication in children under 18 years of age are not available.

Overdose.

Overdose is unlikely due to the low systemic absorption of diclofenac following topical application. In case of accidental ingestion, note that one 45 g tube contains the equivalent of 2.25 g of sodium diclofenac; systemic adverse reactions may occur.

In case of accidental ingestion, gastric lavage and administration of an adsorbent should be performed immediately. Symptomatic treatment using therapeutic measures appropriate for NSAID poisoning is indicated.

Adverse reactions.

The medicinal product is generally well tolerated. Adverse reactions include mild transient skin reactions at the application site. In rare cases, allergic reactions may occur.

Adverse reactions 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 (frequency cannot be estimated from the available data).

Infections and infestations:

very rare – pustular eruptions.

Immune system disorders:

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

Respiratory, thoracic and mediastinal disorders:

very rare – bronchial asthma.

Skin and subcutaneous tissue disorders:

common – rash, erythema, eczema, exanthema, erythema, dermatitis (including contact dermatitis), pruritus, burning sensation, edema, vesicles, papules, pustules, desquamation, and dry skin; rare – bullous dermatitis; very rare – photosensitivity reactions, skin burning sensation, generalized skin eruptions.

Gastrointestinal adverse reactions are very rare after topical application of medicinal products containing diclofenac.

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

Reporting of suspected adverse reactions.

Reporting of suspected adverse reactions after authorization of the medicinal product is extremely important. It allows continuous 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 a temperature not exceeding 25 °C in a place inaccessible to children.

Packaging.

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

Availability.

Over-the-counter (without prescription).

Manufacturer.

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

S.C. SLAVIA PHARM S.R.L.

Manufacturer's address and location of its business operations.

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

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

Marketing authorization holder.

WORLD MEDICINE, LLC, Ukraine.