Diclosef®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DÍCLOSAFE® (DICLOSAFE®)

Composition:

Active substance: diclofenac diethylamine;

1 g of gel contains 11.6 mg of diclofenac diethylamine equivalent to 10 mg of sodium diclofenac;

Excipients: propylene glycol, isopropyl alcohol, carbomer, diethylamine, cocoyl caprylocaprate, oleyl alcohol, cetostearyl polyethylene glycol ether, light mineral oil, butylated hydroxytoluene (E 321), purified water.

Pharmaceutical form. Emulsion gel for topical use.

Main physicochemical characteristics: white or almost white soft homogeneous gel.

Pharmacotherapeutic group. Products used locally for joint and muscular pain. Non-steroidal anti-inflammatory drugs for topical use. Diclofenac. ATC code M02A A15.

Pharmacological properties.

Pharmacodynamics.

Dicloseif® with the active substance diclofenac is a highly effective non-steroidal anti-inflammatory drug (NSAID) for topical use.

Diclofenac is an NSAID that exerts pronounced anti-rheumatic, analgesic, anti-inflammatory, and antipyretic effects. The main mechanism of the therapeutic action of diclofenac is the inhibition of prostaglandin biosynthesis by cyclooxygenase-2 (COX-2).

In inflammation and pain of traumatic or rheumatic origin, the diclofenac gel reduces pain, tissue swelling, and shortens the recovery period of damaged joints, ligaments, tendons, and muscles. Clinical data have shown that diclofenac gel reduces acute pain within 1 hour after the initial application. The drug reduces movement-related pain by 75% within two days. 94% of patients showed a positive response to diclofenac gel after 2 days of treatment, compared to 8% of patients receiving placebo. Relief from pain and functional impairments was achieved after 4 days of treatment with diclofenac gel. Due to its water-alcohol base, the preparation also produces a local anesthetic and cooling effect.

Pharmacokinetics.

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. After topical application of 2.5 g of diclofenac gel to a skin surface area of 500 cm², the absorption rate of diclofenac is approximately 6%. Application of an occlusive dressing for 10 hours leads to a threefold increase in diclofenac absorption.

After application of diclofenac gel to the skin over the joints of the hand and knee, 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. The protein binding of diclofenac is 99.7%.

Diclofenac accumulates in the skin, which acts as a reservoir from which the substance is gradually released into adjacent tissues. From there, diclofenac predominantly enters deeper inflamed tissues, such as joints, rather than into blood plasma. There, it continues to act and is found in concentrations up to 20 times higher than in plasma.

Diclofenac is metabolized primarily via mono- or multi-stage hydroxylation followed by glucuronidation, or by glucuronidation of the intact molecule.

Diclofenac and its metabolites are excreted predominantly in urine. The total systemic plasma clearance of diclofenac is 263 ± 56 ml/min, and the terminal half-life in plasma is on average 1–2 hours. Four metabolites, including two active ones, have short half-lives (1–3 hours), while one has a slightly longer half-life but is practically inactive.

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 other components of the medicinal product.
• History of bronchial asthma, angioedema, urticaria, or acute rhinitis attacks induced by acetylsalicylic acid or other NSAIDs.
• Third trimester of pregnancy.
• Pediatric age under 14 years.

Interaction with other medicinal products and other forms of interaction.

Since systemic absorption of diclofenac following topical administration is very low, the likelihood of interactions is very low. Currently, there are no data on interactions with topical diclofenac. Information on known interactions of oral diclofenac formulations is available in the respective sources.

Special precautions for use

The drug should be used with caution when administered concomitantly with oral NSAIDs.

The possibility of developing systemic adverse effects (which occur with systemic forms of diclofenac) should be considered when the drug is applied over larger skin areas or for longer durations than recommended. In such cases, the medicinal product should be used with caution in patients with hepatic, renal, or cardiac insufficiency, as well as in those with active peptic ulcer disease.

The drug should be used with caution when administered concomitantly with oral NSAIDs, as the frequency of undesirable, especially systemic, adverse effects may increase (see section "Interaction with other medicinal products and other forms of interaction").

Like other drugs that inhibit prostaglandin synthetase, diclofenac and other NSAIDs may cause bronchospasm when used in patients suffering from bronchial asthma or having a history of it.

Diklosayf® gel should only be applied to intact, undamaged areas of skin, avoiding contact with inflamed, injured, or infected skin. Contact of the drug with eyes and mucous membranes should be avoided. The product must not be ingested.

If any skin rash occurs, treatment with the drug should be discontinued.

Diklosayf® gel should not be used under airtight occlusive dressings; however, its use under non-occlusive dressings is permitted.

With topical application of diclofenac, there remains a certain risk of gastrointestinal bleeding in patients who have previously experienced such events.

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.

Patients should be advised not to smoke and to avoid open flames, as this may result in serious burns. Fabrics (clothing, bed linen, wound dressings) that have come into contact with the product can easily ignite and pose a serious fire hazard. Washing clothes and bed linen may reduce gel accumulation but does not completely remove it.

Excipients

Diklosayf® gel contains propylene glycol and butylated hydroxytoluene (BHT). Propylene glycol may cause skin irritation. BHT may cause local skin reactions (e.g., contact dermatitis) or irritation of eyes and mucous membranes.

Use during pregnancy or breastfeeding

Pregnancy

Clinical data on the use of Diklosayf® during pregnancy are lacking. Even though the systemic effect of diclofenac is lower compared to its oral administration, it is unknown whether the systemic exposure to diclofenac achieved after topical application of Diklosayf® could be harmful to the embryo/fetus.

During the first and second trimesters of pregnancy, Diklosayf® 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 cardiopulmonary 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, Diklosayf® is contraindicated during the third trimester of pregnancy (see section "Contraindications").

Breastfeeding period

Like other NSAIDs, diclofenac passes into breast milk in small amounts. However, when therapeutic doses of Diklosayf® gel are used, no effect on breastfeeding is expected. Due to the lack of controlled studies in breastfeeding women, Diklosayf® gel should be used during this period only under medical supervision. During breastfeeding, the product should not be applied to the breasts or large skin areas, nor should it be used for prolonged periods (see sections "Special precautions for use" and "Method of administration and dosage").

Fertility

Data on the effect of topically applied diclofenac on human fertility are lacking.

Ability to affect reaction speed when driving or operating machinery

Diclofenac has no effect when applied topically.

Method of Administration and Dosage

The product is intended for topical use only.

Adults and children aged 14 years and older

Apply Diklosayf® gel 3 to 4 times daily, gently rubbing it into the skin at the site of pain. The amount of the product to be applied depends on the size of the affected area (e.g., 2–4 g, corresponding in size to a cherry or 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 treatment depends on the nature of the condition and the treatment response.

Do not use the product for longer than 14 consecutive days for injuries or soft tissue rheumatism, or longer than 21 days for arthritic joint pain, unless otherwise directed by a physician.

Consult a physician if symptoms do not improve or worsen after 7 days of treatment.

Elderly Patients

The standard adult dosage may be used.

When applying Diklosayf® gel to large areas of the body, systemic absorption of diclofenac will be higher, increasing the risk of adverse reactions, especially if the product is used frequently.

Children

There is insufficient data on the efficacy and safety of Diklosayf® in children under 14 years of age (see section "Contraindications").

If the product is used in children aged 14 years and older for longer than 7 days, or if symptoms worsen, medical advice should be sought.

Overdose

Symptoms

Overdose is unlikely due to the low systemic absorption of diclofenac following topical application. However, systemic adverse reactions may occur if Diklosayf® gel is accidentally ingested (note that one 30-g tube contains the equivalent of 0.3 g of diclofenac sodium).

Treatment

In case of accidental ingestion of the product and the development of significant systemic adverse reactions, general therapeutic measures for NSAID poisoning should be applied. Gastric lavage and administration of activated charcoal are recommended, especially if ingestion occurred recently.

Management of NSAID overdose involves supportive and symptomatic therapy. There is no typical clinical picture associated with diclofenac gel overdose. Supportive and symptomatic treatment should be provided for complications such as arterial hypotension, renal failure, seizures, gastrointestinal disturbances, and respiratory depression. Forced diuresis, hemodialysis, or hemoperfusion are unlikely to be beneficial in eliminating NSAIDs, as the active substances are highly protein-bound and undergo extensive metabolism.

Adverse Reactions

The frequency categories of adverse reactions are defined as follows: 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); frequency not known (cannot be estimated from the available data).

Infections and infestations: very rare – pustular rash.

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, pruritus, eczema, erythema, dermatitis, including contact dermatitis; rare – bullous dermatitis; very rare – photosensitivity reactions; frequency not known – desquamation, skin discoloration, skin burning sensation.

If adverse reactions occur, treatment should be discontinued and medical advice should be sought.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions after the medicinal product has been authorized is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System 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.

Tubes of 30 g, 50 g or 100 g. One tube per cardboard pack.

Supply classification.

Over-the-counter (without prescription).

Manufacturer.

Kusum HealthCare Pvt Ltd /
Kusum Healthcare Pvt Ltd.

Manufacturer's address and location of operations.

SP-289 (A), RIICO Industrial Area, Chopanki, Bhiwadi, Dist. Alwar (Rajasthan), India /
SP-289 (A), RIICO Industrial area, Chopanki, Bhiwadi, Dist. Alwar (Rajasthan), India.