Diclac® long

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DICLAC® LONG (DICLAC® LONG)

Composition:

Active substance: diethylamine diclofenac;

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

Excipients: propylene glycol, oleyl alcohol, isopropyl alcohol, butylhydroxytoluene (E 321), diethylamine, light mineral oil, polyethylene glycol (macrogol) cetearyl ether, coco-capric caprate, flavor "Cream 45399", purified water.

Pharmaceutical form. Gel.

Main physicochemical characteristics: viscous white gel with a characteristic odor.

Pharmacotherapeutic group. Topical preparations used in joint and muscular pain. Nonsteroidal anti-inflammatory drugs for topical use. Diclofenac.

ATC code M02A A15.

Pharmacological Properties

Pharmacodynamics

Diclofenac is a non-steroidal anti-inflammatory agent with pronounced anti-rheumatic, analgesic, anti-inflammatory, and antipyretic effects. The primary mechanism of action is inhibition of prostaglandin biosynthesis via cyclooxygenase-2 (COX-2).

Diclac® Long gel is intended for topical use and has anti-inflammatory and analgesic properties. In cases of inflammatory or rheumatic pain and trauma, the gel relieves pain and swelling, improves patient mobility, and accelerates return to normal daily activities.

Due to its water-alcohol base, the gel also produces a cooling effect.

Pharmacokinetics

Absorption

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 of the medicinal product Diclac® Long (twice daily) over a skin surface area of 400 cm², systemic absorption of the drug, determined as the concentration of the active substance in blood plasma, is equivalent to that observed with application of a diclofenac gel containing 10 mg/g applied four times daily.

The relative systemic bioavailability of diclofenac (calculated based on AUC ratios) was 4.5% on day 7 of treatment following application of the gel containing 23.2 mg of diclofenac diethylamine, compared to oral administration of equivalent doses of sodium diclofenac tablets. Absorption is not affected by the use of an occlusive, vapor-permeable dressing.

Diclac® Long contains an excipient that enhances absorption (oleyl alcohol). In an in vitro study evaluating skin penetration, a gel containing 23.2 mg/g of diclofenac diethylamine was compared with a gel containing 10 mg/g of diclofenac; both formulations were applied at a single dose of 20 mg/cm². After 24 hours, results showed approximately threefold higher cumulative transdermal absorption of diclofenac for the gel containing 23.2 mg/g of diclofenac diethylamine (6.11 ± 1.27 µg/cm²) compared to the gel containing 10 mg/g of diclofenac (2.07 ± 0.38 µg/cm²). Similar results were obtained in another study.

Distribution

After application of Diclac® Long to the skin overlying the wrist and knee joints, diclofenac is detected in plasma (where its maximum concentration is approximately 100 times lower than after oral administration of the same amount of diclofenac), as well as in synovial membrane and synovial fluid.

99.7% of diclofenac is bound to plasma proteins, primarily to albumin (99.4%).

Diclofenac accumulates in the skin, which acts as a reservoir from which the drug is gradually released into adjacent tissues. From there, diclofenac predominantly reaches deeper inflamed tissues such as joints and ligaments, where its concentrations may exceed plasma levels by up to 20 times.

Metabolism

Diclofenac is partially metabolized via glucuronidation and primarily via hydroxylation, forming several phenolic metabolites, two of which are pharmacologically active but significantly less so than diclofenac.

Excretion

Diclofenac and its metabolites are primarily excreted in urine. Total systemic clearance of diclofenac from plasma is 263 ± 56 mL/min. The terminal half-life of diclofenac in plasma averages 1–2 hours. Four metabolites, including two active ones, also have short elimination half-lives of 1–3 hours. One metabolite—3´-hydroxy-4´-methoxydiclofenac—has a longer half-life but is practically inactive.

Renal and Hepatic Impairment

In renal impairment, accumulation of diclofenac and its metabolites does not occur. In chronic hepatitis or decompensated liver cirrhosis, the kinetics and metabolism of diclofenac remain unchanged.

Clinical characteristics

Indications. The medicinal product is indicated for adults and adolescents aged 14 years and older for topical treatment of pain, inflammation, and swelling associated with:

• soft tissue injuries due to trauma, sprains, contusions (including sports injuries);
• episodic back pain, torticollis, and other muscle spasms resulting from physical exercise or other physical exertions.

Contraindications

Hypersensitivity to diclofenac or any of the excipients of the medicinal product.

History of asthma attacks, angioedema, urticaria, or acute rhinitis provoked by acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs.

Do not apply to damaged skin (wounds, eczematous lesions, burns) or mucous membranes.

Do not use in children and adolescents under 14 years of age.

Contraindicated during the third trimester of pregnancy.

Interaction with other medicinal products and other forms of interaction

Since systemic absorption of diclofenac following topical application of the product is very low, drug interactions are unlikely. Concomitant use of Diclac® Long with other systemic nonsteroidal anti-inflammatory drugs or corticosteroids may increase the frequency of adverse effects.

Special precautions for use

Do not apply to large areas of skin. Apply exclusively to the affected area. Use with caution when used concomitantly with oral nonsteroidal anti-inflammatory drugs (NSAIDs).

When applying the medicinal product to large areas of skin or for longer than recommended, consider the possibility of developing systemic adverse reactions typical of systemic diclofenac formulations.

Diclac® Long should be applied only to intact, undamaged skin, avoiding contact with injured (wounded or infected) skin. Contact of the product with eyes and mucous membranes should be avoided. The medicinal product must not be taken orally.

If any skin rash occurs, treatment with the product should be discontinued. The treated area should be protected from exposure to sunlight to reduce the risk of photosensitivity reactions (which may result in skin damage such as eczema, vesiculobullous eruptions, etc.).

Diclac® Long must not be used under airtight occlusive dressings, but application under non-occlusive dressings is permitted.

The product contains light mineral oil (paraffin), which is potentially flammable when accumulated on fabrics (clothing, bed linen, wound dressings, etc.). Washing clothes and bed linen may reduce accumulation of the product but will not completely remove it. Patients should be instructed to exercise caution when smoking or being near open flames due to the risk of severe burns.

Use during the first and second trimesters of pregnancy is not recommended, except when medically justified (see section "Use during pregnancy or breastfeeding").

Diclac® Long contains propylene glycol, which may cause mild localized skin irritation in some individuals, and butylated hydroxytoluene (BHT), which may cause localized skin reactions (e.g. contact dermatitis) or irritation of the eyes and mucous membranes.

Use during pregnancy or breastfeeding

Systemic concentrations of diclofenac are lower after topical application compared to oral formulations. The recommendations below are based on experience with nonsteroidal anti-inflammatory drugs (NSAIDs) that have systemic absorption.

Pregnancy

There are no clinical data on the use of Diclac® Long during pregnancy.

Even though systemic effects are lower than with oral administration, it is unknown whether the systemic exposure to Diclac® Long achieved after topical application could be harmful to the embryo/fetus. During the first and second trimesters of pregnancy, Diclac® Long 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 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, Diclac® Long is contraindicated during the last trimester of pregnancy (see section "Contraindications").

Breastfeeding

Diclofenac passes into breast milk in small amounts. However, when Diclac® Long is used at therapeutic doses, no effect on the breastfed infant is expected. Due to the lack of controlled studies in breastfeeding women, the product should be used during breastfeeding only on medical advice. In such cases, the gel must not be applied to the breasts, nor should it be used on large skin areas or for prolonged periods (see section "Special precautions for use").

Effects on ability to drive and use machines
Topical application of diclofenac does not affect or has negligible effect on the ability to drive a vehicle or operate machinery.

Dosage and Administration

The medicinal product is intended for topical use only.

For adults and children aged 14 years and older, apply the gel twice daily (preferably in the morning and evening), gently rubbing it into the skin—the analgesic effect lasts up to 12 hours. The amount of gel applied depends on the size of the affected area and is approximately 2–4 g (containing 46.4–92.8 mg of diclofenac diethylammonium), which corresponds in volume to a cherry or a walnut. This amount is sufficient for application to an area of 400–800 cm².

Elderly patients (aged 65 years and older). The standard adult dose can be used for treatment of elderly patients. Due to the possibility of adverse reactions, elderly patients should be under close medical supervision.

Renal impairment. Dose reduction is not required in patients with renal impairment.

Hepatic impairment. Dose reduction is not required in patients with hepatic impairment.

Duration of treatment depends on symptoms, underlying disease, and clinical response.

• For treatment of muscle, tendon, and connective tissue injuries: the medicinal product may be used by adults without consulting a physician for up to 14 days.
• For treatment of arthritis (only for adults aged 18 years and older): the product may be used without consulting a physician for up to 21 days.

If symptoms do not improve or worsen within 7 days of treatment, medical advice should be sought.

Instructions for use

The medicinal product is intended for topical application.

Apply the gel in a thin layer to the affected areas of the body and gently rub into the skin.

After application, wipe hands with a cotton tissue or absorbent paper and then wash them, unless the hands themselves are the treated area.

Avoid contact with eyes or mouth. Leave the gel on the skin for several minutes before applying a dressing (see also section "Special instructions for use").

Patients should wait until the medicinal product has dried on the skin before taking a shower or bath.

Children

There is insufficient data on the efficacy and safety of using this medicinal product in children under 14 years of age. If children aged 14 years or older require treatment with this medicinal product for more than 7 days for pain relief, or if symptoms worsen, the patient/parents are advised to consult a physician.

Overdose

Due to the low systemic absorption of topical diclofenac, overdose is unlikely. If the recommended dose is significantly exceeded, the gel should be removed from the skin and washed off with water.

However, if the medicinal product is accidentally ingested, adverse effects typical of diclofenac overdose may occur (the contents of one 50 g tube of Diclac® Long are equivalent to 1 g of sodium diclofenac). In such cases, symptomatic treatment should be initiated using therapeutic measures appropriate for poisoning with nonsteroidal anti-inflammatory drugs. Gastric lavage and administration of activated charcoal should be considered, especially within the first hours after ingestion.

There is no known specific antidote.

Side effects

Mild transient skin reactions at the application site may occur during use of the medicinal product. In rare cases, allergic reactions may occur.

The following are the side effects of the medicinal product by system organ class and frequency. Frequency is defined according to the following categories: 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 available data). Within each frequency group, adverse reactions are listed in order of decreasing severity.

Infections and infestations

Rare: pustular rashes.

Immune system disorders

Rare: hypersensitivity reactions (including urticaria), angioedema.

Respiratory system disorders

Rare: bronchial asthma.

Skin and subcutaneous tissue disorders

Common: rash, pruritus, eczema, erythema, dermatitis including contact dermatitis.

Rare: photosensitivity reactions.

Single cases: bullous dermatitis.

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

When this medicinal product is used over large areas of skin or for prolonged periods, systemic adverse reactions (e.g. renal, hepatic or gastrointestinal adverse reactions, systemic hypersensitivity reactions) cannot be excluded.

Reporting of adverse reactions after authorization of the medicinal product is important. It allows continuous monitoring of the benefit-risk balance of the product. Healthcare professionals, pharmacists, patients, and their legal representatives are encouraged to report all suspected adverse reactions and lack of efficacy via the Automated Information System for Pharmacovigilance at: https://aisf.dec.gov.ua.

Shelf life. 24 months.

Storage conditions. Store at temperatures not exceeding 25 °C. Do not refrigerate or freeze. Keep out of reach and sight of children.

Packaging. 50 g or 100 g of gel in a tube; 1 tube per cardboard box.

Availability. Over-the-counter (without prescription).

Manufacturer.

Lek Pharmaceuticals d.d.

Manufacturer's address and place of business.

Verovškova 57, 1526 Ljubljana, Slovenia.