Ketonal

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT KETONAL®

Composition:

Active ingredient: ketoprofen;

1 g of gel contains 25 mg of ketoprofen;

Excipients: carbomers, triethanolamine, 96% ethanol, lavender oil, purified water.

Pharmaceutical form. Gel.

Main physicochemical properties: homogeneous transparent gel.

Pharmacotherapeutic group.

Agents used locally for joint and muscular pain. Topical non-steroidal anti-inflammatory agents. ATC code M02A A10.

Pharmacological Properties.

Pharmacodynamics.

Ketoprofen belongs to the group of nonsteroidal anti-inflammatory drugs (NSAIDs) and is one of the cyclooxygenase inhibitors. The drug exerts analgesic and anti-inflammatory effects due to stabilization of lysosomal membranes, inhibition of lipoxygenase and bradykinin activity, and suppression of macrophage migration. Ketoprofen acts both at the early (vascular phase) and late (cellular phase) stages of the inflammatory reaction.

Pharmacokinetics.

When the gel is applied topically, ketoprofen is absorbed through the skin, reaches the site of inflammation, thus enabling treatment of joint, tendon, ligament, and muscle injuries associated with pain. Systemic absorption is very low (only 5 % of the applied dose). Plasma protein binding is 99 %. The active substance is detected in synovial fluid at therapeutic concentrations; plasma concentration is negligible.

Ketoprofen is metabolized in the liver to form conjugates, which are slowly excreted primarily in the urine. The metabolism of ketoprofen is not altered in elderly patients, in severe renal insufficiency, or in liver cirrhosis.

Clinical characteristics.

Indications.

Post-traumatic pain in muscles and joints. Tendovaginitis.

Contraindications.

• History of hypersensitivity to ketoprofen or to any of the excipients of the medicinal product;
• History of any photosensitization reactions;
• Known hypersensitivity reactions, such as bronchial asthma symptoms, allergic rhinitis, or urticaria following the use of ketoprofen, fenofibrate, tiaprofenic acid, acetylsalicylic acid, or other NSAIDs;
• History of skin allergy symptoms when using ketoprofen, tiaprofenic acid, fenofibrate, UV blockers, or perfumed products;
• 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;
• Do not apply the gel in the presence of pathological skin changes (e.g., weeping dermatoses, skin lesions, rashes, skin injuries, burns, eczema, acne) or skin infections and open wounds;
• Third trimester of pregnancy.

Interaction with other medicinal products and other forms of interaction.

Systemic absorption of ketoprofen following topical application is very low, and there have been no reports of interactions with other medicinal products during treatment with this medicinal product.

Below are interactions identified during the use of oral formulations of ketoprofen or other NSAIDs.

Ketoprofen may inhibit the elimination of methotrexate and lithium salts and reduce the efficacy of certain diuretics, such as thiazides and furosemide. Concomitant use with high doses of methotrexate is not recommended due to decreased methotrexate excretion, which significantly increases its toxicity.

Concomitant use of ketoprofen with acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs may enhance their effects and increase the risk of adverse reactions.

Concomitant use of probenecid and ketoprofen leads to reduced plasma clearance of ketoprofen and decreased protein binding.

Concomitant use with anticoagulants, antiplatelet agents, and glucocorticoids enhances their effects.

Concomitant use of ketoprofen with cardiac glycosides and cyclosporine increases their toxicity due to reduced excretion.

Ketoprofen may reduce the effect of diuretics and antihypertensive drugs and enhance the effect of oral hypoglycemic agents—sulfonylurea derivatives—as well as some anticonvulsants (phenytoin).

Ketoprofen may reduce the efficacy of mifepristone; therefore, at least 8 days should elapse between the end of mifepristone treatment and the initiation of ketoprofen therapy.

Regular monitoring is recommended for patients taking coumarin derivatives.

Special precautions for use.

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

Although systemic adverse effects of ketoprofen are practically absent with topical use, the gel should be used with caution in patients with impaired kidney, heart, or liver function, with a history of peptic ulcer or intestinal inflammation, cerebrovascular hemorrhage, or hemorrhagic diathesis.

Ketonal® gel should not be applied to mucous membranes, the anal or genital area, large areas of skin, under occlusive dressings, or to the skin around the eyes. Avoid contact of the gel with the eyes. Do not exceed the recommended dosage, and do not use the gel concurrently with other topical agents containing ketoprofen or other NSAIDs on the same skin areas.

Areas of skin treated with the product should be protected from sunlight (including UV radiation in solariums) during treatment and for 2 weeks after treatment to minimize any risk of photosensitization. The product should be discontinued immediately if any skin reactions occur, including skin reactions following concomitant use with products containing octocrylene (octocrylene is added to certain cosmetic and hygiene products such as shampoos, after-shave gels, shower gels, lipsticks, creams, including anti-aging creams, makeup removers, and hair lacquers, to prevent their photodegradation).

Hands should be thoroughly washed after each application of the gel. If prolonged rubbing of the gel into the skin is required, surgical gloves should be used.

Topical application of large amounts of gel may provoke systemic adverse effects, including asthma attacks and hypersensitivity reactions such as contact dermatitis, urticaria, and bronchospasm.

Patients with bronchial asthma in combination with chronic rhinitis, chronic sinusitis, and/or nasal polyps have a higher risk of developing allergy to aspirin and/or nonsteroidal anti-inflammatory drugs compared to the general population.

Do not use the gel near open flames, as it contains ethanol.

Use during pregnancy or breastfeeding.

There are no clinical data on the use of topical formulations of Ketonal during pregnancy. Even though systemic exposure is lower compared to oral administration, it is unknown whether the systemic exposure to Ketonal achieved after topical use could be harmful to the embryo/fetus. During the first and second trimesters of pregnancy, Ketonal should not be used except in cases of extreme necessity. 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 Ketonal, may cause cardiopulmonary and renal toxicity in the fetus. Prolonged bleeding may occur in both mother and child towards the end of pregnancy, and labor may be prolonged. Therefore, Ketonal is contraindicated during the last trimester of pregnancy (see section "Contraindications").

Ability to affect reaction rate when driving or operating machinery.

No data available.

Dosage and Administration.

For external use only.

Apply a thin layer of 3–5 cm of gel to the affected skin area 1–2 times daily and gently rub in. The amount of gel depends on the size of the injured area: 5 cm of gel corresponds to 100 mg of ketoprofen, 10 cm corresponds to 200 mg of ketoprofen. The use of occlusive dressings is not recommended.

The treatment duration is 7–10 days. Hands should be washed after applying the gel. Ketalong®, gel, may be used in combination with other dosage forms (capsules, tablets, suppositories). The total maximum daily dose must not exceed 200 mg of ketoprofen, regardless of the dosage form used.

Children.

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

Overdose.

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

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

Accidental oral ingestion of ketoprofen may cause drowsiness, dizziness, nausea, vomiting, and epigastric pain; these symptoms usually resolve with appropriate symptomatic treatment. High doses of ketoprofen following systemic administration may lead to bradypnea, coma, convulsions, gastrointestinal bleeding, acute renal failure, and increased or decreased arterial blood pressure.

Treatment: There is no specific antidote for ketoprofen overdose. Symptomatic treatment with supportive care to maintain vital functions is recommended. Gastric lavage and administration of activated charcoal (the first dose should be given with sorbitol) may be beneficial, especially if symptoms occur within the first 4 hours after overdose or if the ingested dose exceeds the recommended dose by 5–10 times.

Adverse Reactions

Systemic absorption of ketoprofen after topical application is low compared to plasma concentrations following oral administration. However, the possibility of systemic adverse reactions cannot be completely ruled out when the medicinal product is used for prolonged periods over relatively large areas of skin.

Localized skin reactions such as eczema, itching, and burning sensation are the most commonly observed.

The frequency of adverse reactions is defined as follows: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100), rare (≥ 1/10,000, < 1/1000), very rare (< 1/10,000), frequency not known (cannot be estimated from available data).

Immune system disorders: frequency not known – hypersensitivity reactions; anaphylactic reactions, including angioedema, and anaphylaxis have been reported with both systemic and topical use of ketoprofen; bronchospasm, asthma attacks.

Skin and subcutaneous tissue disorders: uncommon – skin irritation, allergic skin reactions, hyperemia, itching, rash, burning sensation; rare – swelling, erythema, eczema (including vesicular, bullous, and flaccular forms), which may spread and become generalized; purpura-like and bullous rash; increased sweating, urticaria, dermatitis (contact, exfoliative); photosensitivity, including severe skin reactions following sun exposure; purpura, erythema multiforme, lichenoid dermatitis, skin necrosis, Stevens-Johnson syndrome. There have been reports of localized skin reactions that subsequently extended beyond the site of application, as well as of toxic epidermal necrolysis.

Gastrointestinal disorders: very rare – nausea, vomiting, heartburn, constipation (with prolonged use), diarrhea, peptic ulcer, gastrointestinal bleeding.

Renal and urinary disorders: a case of worsening renal function has been described in a patient with chronic kidney insufficiency following topical application of ketoprofen. Interstitial nephritis has occurred in isolated cases.

Depending on the permeability of the active substance, the amount of gel applied, the size of the treated area, the integrity of the skin, the duration of treatment, and the use of occlusive dressings, other hypersensitivity reactions, as well as adverse reactions affecting the gastrointestinal and urinary systems, may occur. Elderly patients are more susceptible to adverse reactions when using nonsteroidal anti-inflammatory drugs.

Ketoprofen may provoke asthma attacks in patients hypersensitive to acetylsalicylic acid or its derivatives.

Shelf life. 3 years.

Storage conditions.

Store at temperatures not exceeding 25 °C.

Keep out of reach of children.

Packaging.

50 g of gel in a tube; 1 tube in a cardboard box.

Prescription status. Prescription only.

Manufacturer.

SALUTAS Pharma GmbH.

Manufacturer's address and site of production.

Production unit in Osterweddingen, Lange Herren 3, Sülzetal, OT Osterweddingen, Saxony-Anhalt, 39171, Germany.