Dicloseif® forte

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DICLOSAFE® FORTE

Composition:

Active substance: diclofenac diethylamine;

1 g of gel contains 23.2 mg of diclofenac diethylamine, equivalent to 20 mg of sodium diclofenac;

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

Pharmaceutical form. Emulsion gel for external use.

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

Pharmacotherapeutic group. Agents used locally in joint and muscle pain. Non-steroidal anti-inflammatory agents for topical use. Diclofenac. ATC code M02A A15.

Pharmacological properties.

Pharmacodynamics.

Diclosafe® Forte with the active substance diclofenac is a 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 gel with diclofenac reduces pain, tissue swelling, and shortens the recovery period of functions in damaged joints, ligaments, tendons, and muscles.

Clinical data have shown that in ankle ligament sprains, the diclofenac gel significantly reduced pain during movement compared to patients receiving placebo, over three days following the start of treatment, including in the subgroup of patients with severe pain. In addition, treatment with this medication also significantly improved ankle joint function within three days after the start of treatment.

Due to its water-alcohol base, the diclofenac gel 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 on both the total applied dose of the drug and the degree of skin hydration. After topical application (twice daily) to a skin surface area of 400 cm², the extent of systemic absorption of the drug, determined as the concentration of the active substance in blood plasma, is equivalent to the application four times daily of diclofenac diethylamine at a concentration of 1.16%.

The relative systemic bioavailability of diclofenac when applying the diclofenac gel on day 7 is 4.5% compared to 50 mg tablets (at the same dose of sodium diclofenac). Absorption does not depend on the use of an occlusive, moisture- and vapor-permeable dressing.

After application of the diclofenac gel to the skin over hand and knee joints, diclofenac is detected in blood plasma (where its maximum concentration is approximately 100 times lower than after oral administration of the same amount of diclofenac), in the synovial membrane, and in synovial fluid. Protein binding of diclofenac is 99.7%, primarily to albumin (99.4%).

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 and ligaments, where it continues to act and is found at concentrations up to 20 times higher than in blood plasma.

Diclofenac is partially metabolized via glucuronidation and primarily via hydroxylation, forming several phenolic derivatives, two of which are pharmacologically active but to a much lesser extent than diclofenac.

Diclofenac and its metabolites are primarily excreted in urine. The terminal half-life of diclofenac from blood plasma averages 1–2 hours. Four metabolites, including two active ones, also have short half-lives—1–3 hours. One of the metabolites—3´-hydroxy-4´-methoxydiclofenac—has a longer half-life but is nearly inactive.

Accumulation of diclofenac and its metabolites in the body is not observed in renal insufficiency. The kinetics and metabolism of diclofenac remain unchanged in chronic hepatitis or decompensated liver cirrhosis.

Clinical characteristics.

Indications.

Treatment of pain, inflammation, and swelling associated with:

• Soft tissue injuries: injuries of tendons, ligaments, muscles, and joints (e.g., due to sprains, strains, contusions) and back pain (sports injuries);
• Localized forms of soft tissue rheumatism: tendinitis (including "tennis elbow"), bursitis, shoulder syndrome, and periarthropathy.

Symptomatic treatment of osteoarthritis of superficial small and medium-sized joints, such as finger joints or knee joints.

Contraindications.

• Hypersensitivity to diclofenac, acetylsalicylic acid, other NSAIDs, or any of the excipients of the drug.
• History of bronchial asthma, angioedema, urticaria, or acute rhinitis attacks induced by acetylsalicylic acid or other NSAIDs.
• Third trimester of pregnancy.
• Age under 14 years.

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 likelihood of interactions is very low. Currently, there are no data on interactions of diclofenac with topical use. However, possible interactions known for oral formulations of diclofenac should be taken into account. Concomitant use of Dikloseif® Forte with other systemic NSAIDs and corticosteroids may increase the frequency of adverse effects.

Special precautions for use.

Use Diclosaif® Forte with caution when combined with oral NSAIDs.

The possibility of developing systemic adverse effects (which may occur with topical application of systemic diclofenac formulations) should be considered when the drug is applied to large areas of skin or for longer durations than recommended.

Diclosaif® Forte gel should be applied only to intact, undamaged areas of skin, avoiding contact with injured (wounded or infected) skin. Contact of the drug with eyes and mucous membranes should be avoided. The product must not be swallowed.

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

Diclosaif® Forte gel should not be used under occlusive, air-tight dressings; however, its application under non-occlusive dressings is permitted.

In patients with peptic ulcer disease (current or in history), there is some risk of gastrointestinal bleeding even with topical application of diclofenac.

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

Due to the possibility of photosensitivity reactions, exposure to direct sunlight should be avoided.

Patients should be advised not to smoke and to avoid open flames, as this poses a risk of severe burns. Fabrics (clothing, bed linen, dressings) that have been in contact with the product can easily ignite and represent a serious fire hazard. Laundering clothing and bed linen may reduce gel accumulation but does not completely eliminate it.

Excipients

Diclosaif® Forte 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.

There are no clinical data on the use of Diclosaif® Forte during pregnancy. Even though systemic effects of diclofenac are lower compared to oral administration, it is unknown whether the systemic exposure to diclofenac achieved after topical application of Diclosaif® Forte could be harmful to the embryo/fetus.

During the first and second trimesters of pregnancy, Diclosaif® Forte 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, Diclosaif® Forte 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, no adverse effects on breastfeeding are expected with therapeutic doses of Diclosaif® Forte gel. Due to the lack of controlled studies in breastfeeding women, Diclosaif® Forte gel should be used during this period only under medical supervision. During breastfeeding, the product should not be applied to the breasts or to large skin areas, nor should it be used for prolonged periods (see sections "Special precautions for use" and "Dosage and administration").

Fertility.

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

Ability to affect reaction speed while driving or operating machinery.

The drug has no effect or has negligible effect on the ability to drive vehicles or operate machinery.

Method of Administration and Dosage

The product is intended for topical use only.

Adults and children aged 14 years and older

Apply DicloSef® Forte gel twice daily (in the morning and evening), gently rubbing it into the skin at the site of pain. The amount of product used depends on the size of the affected area (e.g., 2–4 g, corresponding in size to a cherry or a walnut, is sufficient for application to an area of 400–800 cm²). Analgesic effect lasts up to 12 hours.

Hands should be washed after application, except when the treated area is the hands themselves.

The duration of treatment depends on the nature of the condition and treatment response.

The product should not be used for longer than 14 consecutive days in cases of injuries or soft tissue rheumatism, or longer than 21 days in cases of 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

No dose adjustment is required.

When applying DicloSef® Forte gel to large areas of the body, systemic absorption of diclofenac will be higher, increasing the risk of adverse reactions, especially with frequent use.

Children

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

If the medicinal product is used in children aged 14 years and older for longer than 7 days, or if symptoms worsen, consult a physician.

Overdose

Symptoms

Overdose is unlikely due to low systemic absorption of diclofenac following topical application. However, systemic adverse reactions may occur following accidental ingestion of DicloSef® Forte gel (note that one 30 g tube contains the equivalent of 0.6 g of diclofenac sodium).

Treatment

In case of accidental ingestion and 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 is indicated for complications such as arterial hypotension, renal failure, seizures, gastrointestinal disturbances, and respiratory depression. Forced diuresis, hemodialysis, or hemoperfusion are unlikely to be beneficial for elimination of NSAIDs, as the active substances are highly protein-bound and undergo extensive metabolism.

Adverse reactions.

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

The frequency categories of adverse reactions are defined as follows: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); rare (≥ 1/10000, < 1/1000); very rare (< 1/10000); frequency not known (cannot be estimated from available data).

Infections and infestations: very rare – pustular rash.

Immune system disorders: very rare – hypersensitivity reactions (including urticaria), angioedema.

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 suspected adverse reactions after authorization of the medicinal product 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 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.

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

Availability category.

Over-the-counter (without prescription).

Manufacturer.

Kusum Healthcare Pvt Ltd.

Manufacturer's address and location of business activity.

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