Ketum-gel

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT KETUM-GEL (KETUM-GEL)

Composition:

Active ingredient: 1 g of gel contains 25 mg of ketoprofen;

Excipients: carbomer, methylparaben (E 218), propylparaben (E 216), diethylamine, isopropyl alcohol, polyethylene glycol, purified water.

Pharmaceutical form. Gel.

Main physicochemical properties: clear colorless mass.

Pharmacotherapeutic group.

Non-steroidal anti-inflammatory drugs for topical use. ATC code M02A A10.

Pharmacological Properties.

Pharmacodynamics.

Ketoprofen exerts anti-inflammatory and analgesic effects.

Ketoprofen inhibits the activity of cyclooxygenase-1 and cyclooxygenase-2, thereby reducing the synthesis of prostaglandins, which play a key role in the pathogenesis of inflammation and pain. The mechanism of the anti-inflammatory action of ketoprofen is not fully understood. It reduces oxygen metabolism in neutrophils and release of lysosomal enzymes, inhibits macrophage migration, and exhibits anti-bradykinin activity. These properties allow for reduction of the second phase of the inflammatory response by decreasing migration of macrophages and granulocytes into the synovial membrane and formation of cellular exudates.

Pharmacokinetics.

Ketoprofen penetrates well through the skin and exerts local anti-inflammatory and analgesic effects. Absorption and distribution depend on the thickness of the skin, subcutaneous tissue, its blood supply, as well as the extent of inflammatory infiltrates. After topical application, the concentration of ketoprofen at the site of application is similar to that achieved with systemic administration, while the plasma concentration shows a 60-fold reduction. The bioavailability of the gel is approximately 5%. About 99% of absorbed ketoprofen is protein-bound in plasma. The drug is metabolized in the liver. Approximately 80% of the dose is excreted in urine as metabolites, less than 10% is excreted unchanged. It does not accumulate in the body.

Clinical characteristics.

Indications.

Post-traumatic pain in muscles and joints, tendon inflammation.

Contraindications.

• History of hypersensitivity to ketoprofen or to any of the excipients of the medicinal product;
• History of photosensitization reactions;
• Known hypersensitivity reactions, such as bronchial asthma, allergic rhinitis, or urticaria; history of skin allergy symptoms occurring after use of ketoprofen, fenofibrate, tiaprofenic acid, acetylsalicylic acid, or other nonsteroidal anti-inflammatory drugs, UV blockers, or perfumed products;
• Active peptic ulcer of the stomach or duodenum; history of gastrointestinal bleeding; chronic dyspepsia (discomfort and pain in the upper abdomen);
• Exposure to sunlight (even diffused light) or UV irradiation in a solarium during treatment with the gel and for 2 weeks after discontinuation of treatment;
• Weeping dermatoses, skin damage, rashes, eczema and acne, skin trauma, burns, skin infections, and open wounds;
• Do not apply to mucous membranes, areas around the eyes, or to the anal and genital regions;
• Do not use under occlusive dressings;
• Third trimester of pregnancy;
• Age under 15 years.

Interaction with other medicinal products and other types of interactions.

Since the plasma concentration of the drug is extremely low, symptoms of interaction with other drugs (similar to those with systemic use) are possible only with frequent and prolonged application:

• with methotrexate, cardiac glycosides, lithium salts, cyclosporine – increased toxicity due to reduced excretion;
• with anticoagulants, antithrombotic agents, acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs, glucocorticoids, oral hypoglycemic agents, phenytoin – enhanced effect of the aforementioned drugs; simultaneous use of the drug with other topical formulations (ointments, gels) containing ketoprofen or other nonsteroidal anti-inflammatory drugs is not recommended;
• with antihypertensive agents, diuretics, mifepristone – reduced effect of the aforementioned drugs. At least 8 days must elapse between the end of mifepristone treatment and the start of ketoprofen therapy.

Concomitant use of acetylsalicylic acid and ketoprofen reduces the protein binding of ketoprofen in plasma.

Simultaneous use of probenecid and ketoprofen leads to decreased plasma clearance of ketoprofen and reduced extent of its protein binding.

Monitoring is recommended for patients concurrently receiving coumarin derivatives.

Special precautions for use.

The product is intended for external use only. If a dose of gel is missed, do not double the dose at the next application.

Avoid contact of the product with mucous membranes, areas around the eyes, and eyes.

Do not apply the gel to the anal or genital areas.

Do not use on damaged skin areas (e.g., eczema, acne, infectious processes, or open wounds).

The product should be used with caution and under medical supervision in patients taking anticoagulants, diuretics, or lithium salts.

Exposure to sunlight (even on cloudy days) or UV radiation in solariums during topical application of ketoprofen may cause potentially serious skin reactions (photosensitization).

To avoid the risk of photosensitization, it is necessary to:

• protect from sunlight (including UV radiation in solariums) the skin areas to which the product has been applied, both during treatment and for two weeks after discontinuation;
• thoroughly wash hands after each topical application of ketoprofen.

Treatment should be discontinued immediately if any skin reactions occur after application of the product, including skin reactions following concomitant use with products containing octocrylene (octocrylene is an ingredient in some cosmetic and hygiene products such as shampoos, after-shave gels, shower gels, creams, lipsticks, anti-aging creams, makeup removers, hair lacquers, used to prevent their photodegradation).

The gel should be used with caution in patients with cardiovascular, hepatic, or renal disorders, including severe renal insufficiency, and bronchial asthma. There have been reports of isolated cases of systemic adverse reactions associated with renal impairment. Topical application of large amounts of the product may lead to systemic effects such as hypersensitivity and asthma. The recommended amount of gel and duration of treatment should not be exceeded, as this increases the risk of developing contact dermatitis and photosensitization reactions over time.

In addition, the following precautions should be observed:

• the gel should not be applied to large skin areas or under occlusive dressings;
• if prolonged use of the gel is required, surgical gloves should be used.

Excipients.

The product contains methylparaben (E 218) and propylparaben (E 216), which may cause allergic reactions (possibly delayed).

Propylene glycol, an ingredient of the product, may cause skin irritation.

Use during pregnancy or breastfeeding.

First and second trimesters of pregnancy. Since safety studies of ketoprofen use in pregnant women have not been conducted, its use should be avoided during the first and second trimesters of pregnancy.

Third trimester of pregnancy. All prostaglandin synthesis inhibitors, including ketoprofen, may cause toxic effects on the fetal cardiopulmonary system and kidneys. At the end of pregnancy, prolonged bleeding time may occur in both mother and child. Nonsteroidal anti-inflammatory drugs may delay the onset of labor. Therefore, the use of ketoprofen is contraindicated during the third trimester of pregnancy.

Following systemic administration (oral, rectal, parenteral), traces of ketoprofen are found in breast milk. Ketoprofen should not be used during breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

Data are lacking.

Dosage and Administration.

For external use only.

Apply a small amount of gel (3–5 cm) to the affected area of skin 2–3 times daily and gently rub in. The duration of treatment is determined individually by a physician.

There is no need to apply a dry dressing, as the gel is well absorbed through the skin, is odorless, contains no dyes, does not leave greasy stains, and does not soil clothing.

After applying the gel, hands should be washed unless the gel has been applied directly to the hands. Surgical gloves should be used if prolonged rubbing into the skin is necessary.

Children.

The safety and efficacy of the medicinal product have not been established in this age group.

Overdose.

Symptoms: irritation, erythema, itching, or worsening of other adverse reactions.

Since the amount of ketoprofen penetrating through the skin into blood plasma is low, overdose is unlikely. Systemic adverse reactions may occur with prolonged use, high doses, or application over large areas of skin. If excessive amounts of gel have been applied, the skin should be washed with water.

In case of accidental oral intake of ketoprofen, the drug may cause drowsiness, nausea, and vomiting. High doses of ketoprofen with systemic administration may lead to respiratory depression, coma, convulsions, gastrointestinal bleeding, acute renal failure, and increased or decreased arterial blood pressure.

Treatment: there is no specific antidote; symptomatic treatment together with supportive care of vital functions is recommended. Gastric lavage and administration of activated charcoal (the first dose should be given with sorbitol) are recommended, especially within the first 4 hours after overdose or after ingestion of a dose 5–10 times higher than the recommended dose.

Side effects

The side effects are listed by 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 from the available data).

Infections and infestations: frequency not known – secondary impetigo.

Blood and lymphatic system disorders: frequency not known – eosinophilia.

Immune system disorders: frequency not known – anaphylactic reactions, including anaphylactic shock, angioedema, hypersensitivity reactions reported with systemic and topical use of ketoprofen.

Respiratory, thoracic and mediastinal disorders: frequency not known – bronchospasm, bronchial asthma attacks.

Eye disorders: frequency not known – eyelid edema.

Vascular disorders: frequency not known – vasculitis.

Gastrointestinal disorders: frequency not known – heartburn, nausea, vomiting, diarrhea, constipation, lip swelling, peptic ulcer, gastrointestinal bleeding.

Skin and subcutaneous tissue disorders: uncommon – hyperemia; pruritus; rash; burning sensation, erythema, eczema; rare – allergic skin reactions; purpura-like, bullous rash; urticaria, dermatitis (contact, exfoliative, bullous); eczema, including vesicular, bullous and bullous-erosive forms, which may spread and become generalized; photosensitivity reactions, including severe skin reactions following sun exposure; skin desquamation, skin swelling;

frequency not known – skin irritation, increased sweating, purpura, erythema multiforme; Stevens-Johnson syndrome; skin necrosis. There have been reports of local skin reactions that may extend beyond the application site, including toxic epidermal necrolysis.

Renal and urinary disorders: very rare – worsening of renal dysfunction or renal failure, particularly in patients with chronic renal failure, interstitial nephritis.

General disorders and administration site conditions: frequency not known – fever.

Injury, poisoning and procedural complications:* frequency not known – wound complications.

Depending on the penetrative ability of the active substance, the amount of gel applied, the size of the treated area, the integrity of the skin, the duration of use of the medicinal product, and the use of occlusive dressings, other hypersensitivity reactions, gastrointestinal and urinary system side effects may occur. Elderly patients are more susceptible to side effects when using nonsteroidal anti-inflammatory drugs.

Ketoprofen may trigger bronchial asthma attacks in patients with hypersensitivity to acetylsalicylic acid or its derivatives.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions after registration of the medicinal product is important. This allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report all suspected adverse reactions to the State Expert Centre of the Ministry of Health of Ukraine.

Shelf life. 2 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

50 g of gel in tubes, 1 tube per carton.

Prescription category. Prescription only.

Manufacturer.

Mepro Pharmaceuticals Private Limited.

Address.

Unit II, Q-Road, Phase IV, GIDC, Wadhwan, Surendranagar, Gujarat, 363 035, India /
Unit II, Q-Road, Phase IV, GIDC, Wadhwan, Surendranagar, Gujarat, 363 035, India.