Diclofenac-teva forte 2 %

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Diclofenac-Teva Forte 2% (Diclofenac-Teva Forte 2%)

Composition:

Active substance: diclofenac diethylamine;

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

Excipients: isopropyl alcohol, propylene glycol (E 1520), caprylic/capric cocoate, mineral oil, carbomer 974P, polyethylene glycol cetyl stearyl ether 22, diethylamine, flavor (camphor, eucalyptol, ambroxide, citronellol, benzyl alcohol, citral, coumarin, eugenol, farnesol, geraniol, limonene, linalool), oleic acid (E 570), butylated hydroxytoluene (E 321), purified water.

Pharmaceutical form. Gel.

Main physicochemical properties: homogeneous cream-like gel, white to almost white in color.

Pharmacotherapeutic group. Agents used locally for joint and muscular pain. Topically applied non-steroidal anti-inflammatory drugs. Diclofenac.

ATC code M02A A15.

Pharmacological Properties

Pharmacodynamics

Diclofenac is a nonsteroidal anti-inflammatory agent with pronounced anti-rheumatic, analgesic, anti-inflammatory, and antipyretic effects. Its primary mechanism of action is the inhibition of prostaglandin biosynthesis via cyclooxygenase-2.

Diclofenac reduces inflammation-induced pain, swelling, and fever, and reversibly inhibits ADP- and collagen-induced platelet aggregation. Clinical studies have demonstrated a statistically significant and clinically meaningful reduction in pain during movement within three days of initiating treatment, as well as noticeable improvement in lower limb joint function within the first three days of use.

Pharmacokinetics

Absorption

The amount of diclofenac absorbed through the skin is proportional to the application area and depends on the total administered dose of the drug and the degree of skin hydration. After twice-daily topical application over a skin surface area of 400 cm², the extent of systemic absorption, measured as plasma concentration of the active substance, is equivalent to that achieved with four daily applications of 1.16% diclofenac diethylamine gel.

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

Distribution

99.7% of diclofenac is bound to plasma proteins, primarily to albumin (99.4%). After topical application to the skin overlying 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.

Diclofenac accumulates in the skin, which acts as a reservoir, allowing gradual release of the substance into adjacent tissues. From there, diclofenac primarily reaches deeper inflamed tissues such as joints and ligaments. It continues to exert its effect at these sites, where concentrations are up to 20 times higher than in plasma.

Biotransformation

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

Elimination

Diclofenac and its metabolites are primarily excreted in urine. Diclofenac is eliminated from plasma at a systemic clearance rate of 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 half-lives of 1–3 hours. One metabolite—3´-hydroxy-4´-methoxydiclofenac—has a longer half-life but is pharmacologically inactive.

Special patient groups

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

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 dislocation, strain, contusion) 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 or any of the excipients.
• History of bronchial asthma attacks, bronchospasm, angioedema, urticaria, or acute rhinitis induced by acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs (NSAIDs).
• Do not apply to mucous membranes, open wounds, or in the presence of inflammatory and infectious skin diseases such as eczema.
• Children and adolescents under 14 years of age.
• Third trimester of pregnancy.

Interaction with other medicinal products and other forms of interaction.

Since systemic absorption of diclofenac following topical application is very low, drug interactions are unlikely. However, concomitant use of Diclofenac-Teva Forte 2% with systemic NSAIDs or corticosteroids may increase the frequency of adverse effects.

Special precautions for use.

Use with caution in combination with oral nonsteroidal anti-inflammatory drugs.

The possibility of developing systemic adverse reactions (which occur with systemic forms of diclofenac) cannot be excluded when the medicinal product is applied over large skin areas or for longer durations than recommended.

Diclofenac-Teva Forte 2% should be applied only to intact, undamaged skin areas, 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 ingested.

Patients with bronchial asthma, hay fever, mucosal edema (nasal polyps), chronic obstructive pulmonary disease, or chronic respiratory infections (especially if associated with symptoms resembling allergic rhinitis) are more prone to attacks of bronchial asthma (so-called analgesic intolerance, aspirin-induced asthma), Quincke's edema, and urticaria. Precautionary measures (readiness to provide emergency medical assistance) are recommended for such patients. This also applies to patients with allergies to other substances that manifest as skin reactions, itching, or urticaria.

If any skin rash occurs, application of the medicinal product should be discontinued. Patients should be warned against excessive exposure to sunlight to reduce the likelihood of photosensitivity reactions.

Diclofenac-Teva Forte 2% should not be used under occlusive, air-tight dressings; however, application under non-occlusive dressings is permitted.

As a precautionary measure, care should be taken to ensure that children do not come into contact with skin areas to which the gel has been applied.

Diclofenac-Teva Forte 2% contains propylene glycol (E 1520), which may cause mild localized skin irritation in some individuals, as well as butylated hydroxytoluene (E 321), which may cause localized skin reactions (e.g., contact dermatitis) or irritation of the eyes and mucous membranes.

The medicinal product contains benzyl alcohol (0.15 mg/g), citral, citronellol, coumarin, eugenol, farnesol, geraniol, limonene, and linalool, which may cause allergic reactions. Benzyl alcohol may cause moderate local irritation.

Use during pregnancy or breastfeeding.

Pregnancy. There are no clinical data on the use of this medicinal product during pregnancy. Even though systemic exposure after topical application is lower than with oral administration, it is unknown whether the systemic exposure achieved after topical use could be harmful to the embryo/fetus.

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development. Epidemiological data suggest an increased risk of miscarriage and an increased risk of cardiac defects and gastroschisis following exposure to prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiovascular malformations increased from less than 1% to approximately 1.5%. It is assumed that the risk increases with dose and duration of treatment. In animal studies, administration of prostaglandin synthesis inhibitors has been shown to increase pre- and post-implantation loss and embryonic/fetal mortality.

Furthermore, in animals treated with a prostaglandin synthesis inhibitor during organogenesis, an increased incidence of various developmental abnormalities, particularly affecting the cardiovascular system, has been observed.

Diclofenac should be used during the first and second trimesters of pregnancy only if clearly necessary. If diclofenac is used by women attempting to conceive or during the first and second trimesters of pregnancy, the dose of the medicinal product should be as low as possible and the duration of treatment as short as possible.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors, including diclofenac, may affect the fetus as follows:

• cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);
• renal dysfunction, which may progress to renal failure with oligohydramnios; renal toxicity.

Effects on the mother and newborn at the end of pregnancy:

• possible prolonged bleeding time, anti-aggregatory effect, which may occur even at very low doses;
• inhibition of uterine contractions, leading to delayed or prolonged labor.

Therefore, Diclofenac-Teva Forte 2% is contraindicated during the third trimester of pregnancy.

Breastfeeding. Like other NSAIDs, diclofenac passes into breast milk in small amounts. When therapeutic doses of diclofenac are used, no adverse effects on the infant are expected. No studies have been conducted in breastfeeding women; therefore, this medicinal product should be used only on medical advice. Hence, if there are strong reasons for using the gel during breastfeeding, it should not be applied to the breasts or large skin areas and should not be used for prolonged periods.

Ability to influence reaction speed while driving or operating machinery.

Topical application of diclofenac does not affect the ability to drive or operate machinery.

Method of Administration and Dosage

The medicinal product is intended for topical use only.

For adults and children aged 14 years and older, the product is applied twice daily (morning and evening), gently rubbed into the skin at the site of pain localization. Analgesic effect lasts up to 12 hours.

The amount of medicinal product used depends on the size of the affected area
(for example, 2–4 g of gel, corresponding in size to a cherry or a walnut, is sufficient for application to an area of 400–800 cm²). The maximum daily dose of the medicinal product is 8 g (equivalent to 160 mg of diclofenac sodium).

After application, hands should be washed, except when the hands themselves are the treated area.

Before applying a dressing, allow the gel to dry for several minutes.

Duration of therapy depends on the indication and treatment efficacy. The medicinal product should not be used for longer than 14 consecutive days in cases of injuries or soft tissue rheumatism, and not longer than 21 days in cases of arthritic joint pain, unless otherwise directed by a physician.

If the patient's condition does not improve or worsens after 7 days of treatment, medical advice should be sought.

Elderly patients do not require dose adjustment; however, due to the possibility of adverse reactions, they should be carefully monitored.

Patients with renal impairment or hepatic impairment do not require dose adjustment.

Children. Diclofenac-Teva Forte 2% is contraindicated for use in children under 14 years of age.

Overdose

Overdose is unlikely due to the low systemic absorption of diclofenac following topical application. If more gel is applied than recommended, the excess should be washed off with water.

In case of accidental ingestion, adverse effects characteristic of systemic diclofenac reactions may occur (the contents of one 100 g tube of Diclofenac-Teva Forte 2% is equivalent to 2000 mg of diclofenac sodium).

In such cases, if significant systemic adverse reactions occur, therapeutic measures for NSAID poisoning should be implemented. Following accidental ingestion, gastric lavage should be performed immediately and an adsorbent administered. There is no specific antidote.

Adverse reactions.

The adverse reactions listed below are classified by organ systems and frequency. Frequency: 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 based on available data).

Infections and parasitic diseases. Very rare: pustular eruptions.

Immune system disorders. Very rare: hypersensitivity reactions (including urticaria), angioneurotic edema.

Respiratory system disorders. Very rare: bronchial asthma.

Gastrointestinal disorders. Very rare: gastrointestinal complaints.

Skin and connective tissue disorders. Common: dermatitis (including contact dermatitis), rash, erythema, eczema, pruritus. Uncommon: desquamation, skin dryness, edema. Rare: bullous dermatitis. Very rare: photosensitization. Frequency not known: burning sensation at the application site, skin dryness.

When applying the gel to large areas of skin and for prolonged periods, systemic adverse reactions of diclofenac (e.g. affecting the kidneys, liver or gastrointestinal tract, systemic hypersensitivity reactions) cannot be excluded.

Reporting of suspected adverse reactions.

It is important to report suspected adverse reactions after marketing authorization. This allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are required to report any suspected adverse reactions.

Shelf life. 2 years.

Do not use the tube after the expiry date stated on the packaging.

Storage conditions.

No special storage conditions are required. Keep in the original packaging to protect from light. Keep out of the reach of children.

Packaging. 30 g, 50 g, or 100 g of gel in a tube; 1 tube per cardboard box.

Pharmaceutical classification. Over-the-counter (without prescription).

Manufacturer. Merckle GmbH.

Manufacturer's address and location of business operation.

Graf-Arco-Strasse 3, 89079 Ulm, Germany.