Darfen® gel

INSTRUCTIONS for medical use of the medicinal product Darfen® Gel (Darfen gel)

Composition:

active substances: ibuprofen, levomenthol;

1 g of gel contains: ibuprofen 50 mg, levomenthol 30 mg;

excipients: ethanol 96%, propylene glycol, carbomer, diisopropanolamine, purified water.

Pharmaceutical form. Gel.

Main physicochemical characteristics: transparent homogeneous gel with a menthol odor.

Pharmacotherapeutic group

Topical preparations used for joint and muscle pain.

ATC code M02AX10.

Pharmacological Properties

Pharmacodynamics

Darfen® Gel is a combined topical preparation containing ibuprofen and naturally derived menthol. Ibuprofen, a derivative of phenylpropionic acid, belongs to the group of nonsteroidal anti-inflammatory drugs (NSAIDs) and exerts analgesic and anti-inflammatory effects due to inhibition of prostaglandin synthetase. The action of levomenthol, the optical isomer of menthol, is mediated by reflex reactions associated with stimulation of sensitive nerve endings in the skin. Menthol stimulates skin nociceptors, resulting in the release of peptides with vasodilatory effects. The medicinal product produces a counterirritant and stimulating effect, and also helps relieve pain.

Pharmacokinetics

When applied topically, ibuprofen is well and rapidly absorbed through the skin. Only a very small amount reaches the systemic circulation. Maximum plasma concentration of ibuprofen is achieved 2 hours after application and amounts to 0.6 μg/mL. The extent of ibuprofen absorption following topical application is approximately 5% of that observed after oral administration.

Levomenthol absorbed through the skin is transported to the liver. Some phase I metabolism may occur in the skin, but the majority takes place in the liver. Menthol is hydroxylated and then conjugated with glucuronic acid prior to circulation to the kidneys for urinary excretion.

Clinical Characteristics

Indications

Darfen® Gel is recommended for relief of pain and reduction of inflammation in rheumatic, muscular and joint pain, back pain, as well as in pain and swelling caused by injury, ligament sprains, and sports injuries.

Contraindications

The medicinal product is contraindicated:

• in case of hypersensitivity to ibuprofen, levomenthol, acetylsalicylic acid, or any component of the medicinal product, or to other NSAIDs (including oral use);
• in asthma, or in patients with a history of bronchial asthma attacks, urticaria, angioedema (Quincke's edema), or acute rhinitis induced by acetylsalicylic acid or other NSAIDs;
• for application on damaged or denuded (epithelium-free) skin;
• on open wounds, inflammatory or infectious skin diseases such as weeping eczema, and for application on mucous membranes;
• in dermatoses;
• in presence of local infection;
• for simultaneous use on the same area with other topically applied medicinal products;
• in peptic ulceration of the gastrointestinal tract;
• in the third trimester of pregnancy.

Interaction with other medicinal products and other forms of interaction

When used concomitantly with acetylsalicylic acid or other NSAIDs, the risk of adverse effects increases. NSAIDs may interact with antihypertensive drugs, may reduce the diuretic effect of furosemide, and may enhance the effect of anticoagulants, although such likelihood with topical preparations is very low.

Special precautions for use

The medicinal product contains propylene glycol, which may cause skin irritation; therefore, before first use, it is necessary to test the patient's sensitivity to Darfen® Gel on a small area of skin.

It is known that oral ibuprofen may exacerbate renal insufficiency or aggravate active peptic ulcer disease. Patients with impaired renal function, asthma, active peptic ulcer disease of the stomach or duodenum in medical history, and patients undergoing treatment with oral NSAIDs should consult a physician before using this medicinal product. The gel must not be applied to mucous membranes, near mucous membranes, on lips, nostrils, areas around the eyes, genital organs, or the anal opening, as well as on damaged, inflamed, or irritated skin. If the gel comes into contact with these areas, it must be immediately rinsed off thoroughly with a large amount of clean water.

After applying Darfen® Gel, hands must always be washed unless they are the area being treated.

If the medicinal product is accidentally swallowed, the patient must immediately seek medical advice from a physician or the nearest emergency facility.

Airtight dressings must not be applied over the area where the gel has been applied.

Treatment must be discontinued if rash or irritation occurs, and the patient should consult a physician.

Adverse reactions can be minimized by using the lowest effective dose for the shortest possible duration.

If any adverse effects occur, or if there is no improvement or worsening of the condition, the patient must consult a physician.

The use of Darfen® Gel, like other drugs that inhibit cyclooxygenase/prostaglandin synthesis, may impair fertility. However, this likelihood is lower for topically applied NSAIDs compared to oral formulations. For women who have difficulty conceiving or who are undergoing fertility investigations, discontinuation of Darfen® Gel may be advisable.

Patients with bronchial asthma, hay fever, chronic lung disease, or hypersensitivity to analgesics and anti-rheumatic drugs have a higher risk of developing asthma attacks, mucosal swelling (angioedema), or urticaria compared to other patients. Systemic absorption of ibuprofen after topical application is lower than after oral administration; therefore, such complications may occur less frequently. The use of this medicinal product in such patients should be performed under physician supervision.

Severe cutaneous adverse reactions (SCARs), including exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), and acute generalized exanthematous pustulosis (AGEP), which may be life-threatening or lead to fatal outcomes, have been reported during ibuprofen use (see section "Adverse reactions"). Most of these reactions occurred within the first month of treatment.

If signs or symptoms suggestive of these reactions appear, ibuprofen must be discontinued immediately, and alternative treatment options should be considered (if necessary).

Care must be taken to ensure that children do not come into contact with skin areas treated with the medicinal product.

Skin areas treated with the medicinal product should not be exposed to prolonged sunlight to avoid photosensitivity.

During use of the medicinal product, safety precautions must be observed: do not smoke or approach open flames, as there is a risk of severe burns. Any fabric (clothing, bed linen, dressings, etc.) that has come into contact with the medicinal product Darfen® Gel becomes more flammable and poses a serious fire hazard. Washing clothing and bed linen may reduce accumulation of the medicinal product but will not completely eliminate it.

Use during pregnancy or breastfeeding

Clinical data on the use of the topical medicinal product Darfen® Gel during pregnancy are lacking. Even though systemic exposure is lower compared to oral administration, it is unknown whether systemic exposure to Darfen® Gel achieved after topical application could be harmful to the embryo/fetus. Darfen® Gel should not be used during the first and second trimesters of pregnancy 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 synthetase inhibitors, including Darfen® Gel, may cause cardiopulmonary and renal toxicity in the fetus. Prolonged bleeding may occur in both mother and child near the end of pregnancy, and labor may be delayed. Therefore, Darfen® Gel is contraindicated during the last trimester of pregnancy (see section "Contraindications").

Ibuprofen and its metabolites pass into breast milk; therefore, this medicinal product is not recommended during breastfeeding.

Ability to affect reaction speed when driving or operating machinery

Not established.

Method of Administration and Dosage

For external use only.

The sealed opening of the tube must be pierced with the spike located on the upper outer part of the cap.

For each application, use 1–7 cm of gel from a tube containing 50 g or 100 g of gel, and 4–10 cm from a tube containing 15 g of gel.

Apply the gel to the affected painful area and gently rub in until completely absorbed. If necessary, apply up to 3 times daily, but no more frequently than every 4 hours. If there is no improvement after two weeks, consult a physician. A dressing must not be applied over the area where the gel has been applied.

Children

This medicinal product is contraindicated for use in children under 12 years of age.

Overdose

The likelihood of overdose when using ibuprofen in the form of a topical gel is low. However, in case of overdose, adverse effects associated with systemic ibuprofen use may occur (dyspeptic symptoms: nausea, heartburn, vomiting, flatulence; skin allergic reactions; headache, drowsiness, dizziness; arterial hypotension). If symptoms of overdose occur, discontinue use of the medicinal product and consult a physician. In case of exceeding the recommended dose, wash off the gel with water. No specific antidote is known. Correction of the electrolyte balance is indicated.

Side effects

Skin and subcutaneous tissue disorders: hypersensitivity reactions, which may manifest as skin purpura, angioedema, bullous dermatoses (including epidermal necrolysis and erythema multiforme); skin redness, irritation, photosensitivity reactions. Most commonly observed skin disorders include: rash, urticaria, pruritus, dry skin, burning sensation, contact dermatitis. Very rare: severe cutaneous adverse reactions (SCARs) (including erythema multiforme, exfoliative dermatitis, Stevens–Johnson syndrome, and toxic epidermal necrolysis). Frequency not known: drug-induced eosinophilia with systemic symptoms (DRESS syndrome) and acute generalized exanthematous pustulosis (AGEP), photosensitivity reactions.

Respiratory, thoracic and mediastinal disorders: hypersensitivity reactions such as bronchial asthma attacks or worsening of asthma, dyspnea, shortness of breath, and bronchospasm may occur in patients with a history of bronchial asthma or allergic diseases.

Gastrointestinal disorders: depending on the amount of gel applied, the area of application, skin integrity, duration of treatment, and use of occlusive dressing, the following may occur, although unlikely: abdominal pain, dyspepsia.

Renal and urinary disorders: impaired renal function in patients with a history of kidney disease.

Immune system disorders: hypersensitivity reactions, including anaphylactic shock, angioneurotic edema, and non-specific allergic reactions.

Other systemic adverse reactions to NSAIDs depend on the amount of gel applied, the area of application, skin integrity, duration of treatment, and use of occlusive dressing.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, are encouraged to report all suspected adverse reactions and/or lack of efficacy of the medicinal product via the Automated Pharmacovigilance Information System at: 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 of children.

Incompatibilities

Do not use with other topical medicinal products.

Packaging

15 g, 50 g, or 100 g in a tube; 1 tube per carton.

Prescription status

Over-the-counter.

Manufacturer

JSC "Pharmaceutical Company "Darnytsia".

Manufacturer's address and location of its business activity

13, Boryspylska Street, Kyiv, 02093, Ukraine