Valusal

INSTRUCTIONS for medical use of the medicinal product VАLUSAL® (VALUSAL)

Composition:

Active substance: ketoprofen;

1 g of gel contains 25 mg of ketoprofen;

Excipients: ethanol 96%, carbomer, diethanolamine, lavender oil, methyl parahydroxybenzoate (E 218), orange oil, propyl parahydroxybenzoate (E 216), purified water.

Medicinal form: Gel.

Main physicochemical properties: transparent or slightly opalescent, colourless or slightly yellowish gel with a characteristic odour.

Pharmacotherapeutic group:

Non-steroidal anti-inflammatory drugs for topical use.

ATC code: M02A A10.

Pharmacological properties.

Pharmacodynamics.

Ketoprofen belongs to the group of nonsteroidal anti-inflammatory drugs (NSAIDs) with pronounced analgesic effect. The mechanism of action of the drug is associated with reduction of prostaglandin synthesis through inhibition of cyclooxygenase (COX-1 and COX-2) activity. Ketoprofen stabilizes lysosomal membranes, inhibits leukotriene synthesis, and exhibits anti-bradykinin activity. It reduces pain and swelling caused by inflammation.

Pharmacokinetics.

With repeated topical administration of ketoprofen (e.g., 375 mg of ketoprofen), the plasma concentration is approximately 100 times lower than that after single oral administration of 150 mg of ketoprofen.

Ketoprofen is metabolized to acylglucuronides and is primarily excreted in urine. The elimination half-life of ketoprofen after repeated application of the gel averages 17 hours, and bioavailability is approximately 5%.

Clinical characteristics.

Indications.

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

Contraindications.

• Hypersensitivity to ketoprofen or to excipients of the medicinal product, salicylates, or other NSAIDs.
• Known hypersensitivity reactions, such as bronchial asthma, allergic rhinitis, or urticaria following administration of ketoprofen, other NSAIDs, salicylates (e.g., acetylsalicylic acid), fenofibrate, or tiaprofenic acid.
• History of photosensitization reactions.
• History of skin allergy symptoms occurring during application of ketoprofen, excipients of the product, fenofibrate, tiaprofenic acid, UV-blocking agents, or perfumes.
• Exposure to sunlight (even on cloudy days), including indirect sunlight or irradiation in solariums, during the entire treatment period and for at least 2 weeks after discontinuation of the treatment.
• Exacerbation of gastric or duodenal ulcer; gastrointestinal bleeding in history; chronic dyspepsia (discomfort and pain in the upper abdomen).
• Skin lesions, weeping dermatoses, rashes, skin trauma, irritation, pruritus, skin infections, acne, burns. The gel must not be applied to damaged skin (eczema, dermatoses, open or infected wounds).
• Do not use under occlusive dressings.
• Third trimester of pregnancy.
• Use in children.

Interaction with other medicinal products and other forms of interaction.

Since plasma concentrations of ketoprofen are very low after topical application, symptoms of interaction with other drugs (similar to those observed with systemic administration) are possible only with frequent and prolonged use:

• With methotrexate, cardiac glycosides, lithium salts, cyclosporine – increased toxicity due to reduced excretion;
• With anticoagulants, antiplatelet agents, acetylsalicylic acid or other NSAIDs, glucocorticoids, oral hypoglycemic agents, phenytoin – enhanced effect of the aforementioned drugs; concomitant use of the product with other topical formulations (creams, gels) containing ketoprofen or other NSAIDs is not recommended;
• With antihypertensive agents, diuretics, mifepristone – reduced efficacy of the aforementioned drugs. At least 8 days must elapse between the end of mifepristone treatment and initiation of ketoprofen therapy.

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

Simultaneous administration of probenecid and ketoprofen leads to decreased clearance and reduced protein binding of ketoprofen.

Monitoring is recommended in patients concurrently receiving coumarins.

Special precautions for use

Ketoprofen in the form of a gel is intended for topical use only. If a dose is missed, do not double the dose at the next application.

Avoid contact of the gel with mucous membranes, areas around the eyes, and eyes. Hands should be washed after applying the medication.

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

The medicinal product should be used with caution and under physician supervision in patients receiving anticoagulants, diuretics, or lithium salts.

The product should be used with caution in patients with impaired renal or hepatic function, cardiovascular disorders, severe renal insufficiency, bronchial asthma, and also in patients with severe uncompensated heart failure. Patients with asthma associated with chronic rhinitis, sinusitis, or nasal polyps have a higher risk of developing hypersensitivity reactions to aspirin or NSAIDs compared to the general population.

There have been reports of isolated cases of systemic adverse reactions associated with renal impairment. Topical application of large amounts of the drug may lead to such systemic effects as hypersensitivity and asthma.

Do not exceed the recommended dose or duration of treatment, as the risk of contact dermatitis and photosensitivity reactions increases over time.

The product should not be applied over large skin areas or under occlusive dressings.

During treatment and for 2 weeks after treatment, to reduce the risk of photosensitization, skin areas treated with the gel must be protected from sunlight (even on cloudy days) and from UV radiation in solariums. Treatment should be discontinued immediately if any skin reactions occur, including skin reactions following concomitant use with substances containing octocrylene (an excipient found in some cosmetic and hygiene products such as shampoos, after-shave gels, shower gels, creams, lipsticks, anti-aging creams, makeup removers, hair sprays) used to prevent their photodegradation.

Use during pregnancy or breastfeeding

During the first and second trimesters of pregnancy, the medicinal product should be used only after careful assessment of the benefit-risk ratio for the mother and potential risk to the fetus.

During the third trimester of pregnancy, prostaglandin synthesis inhibitors, including ketoprofen, may cause cardiopulmonary and renal toxicity in the fetus. Prostaglandin synthesis inhibitors may also prolong bleeding time in both mother and child; therefore, the gel is contraindicated during the third trimester of pregnancy.

During breastfeeding, use of the gel is not recommended. Breastfeeding should be discontinued for the duration of treatment with ketoprofen.

Ability to influence reaction rate while driving or operating machinery

Data are lacking.

Dosage and Administration

For external use only.

Adults: Apply a small amount of gel (3–5 cm) to the affected area of skin 2–3 times daily and gently rub in. The skin at the painful site must be intact. The amount of gel applied depends on the size of the affected body area.

The daily dose should not exceed 15 g (7.5 g corresponds to 14 cm of gel). The gel should be used in short treatment courses. The duration of treatment depends on the nature and severity of the condition and is determined individually by a physician; typically, the treatment course lasts 1–10 days.

The affected skin area must not be covered with a bandage. Clothing in contact with the treated area should not cause discomfort to the patient. 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. Hands should be washed after applying the gel, except when the gel is applied directly to the hands. Protective gloves should be used if prolonged rubbing into the skin is required.

Elderly patients: There are no data indicating that elderly patients require different dosing.

Children: The gel must not be used in children, as sufficient data on the use of the medicinal product in this age group are lacking.

Overdose

When applied topically, the bioavailability of ketoprofen is low, making overdose unlikely.

With topical application of very large doses, skin irritation, erythema, itching, or worsening of other adverse reactions may occur. If an excessive amount of gel has been applied to the skin, it should be washed off with water.

Systemic adverse effects may occur with incorrect use or accidental overdose.

Accidental oral ingestion of ketoprofen may cause drowsiness, nausea, vomiting, dizziness, epigastric pain, and bradypnea. 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.

There is no specific antidote. 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) are recommended if less than 1 hour has passed since the overdose.

Side effects.

Local reactions.

Local skin reactions may occur, which may spread beyond the area treated with the gel; in isolated cases, they may progress to severe reactions and spread throughout the entire body.

Skin and subcutaneous tissues: erythema, intense itching, burning sensation, eczema, including vesicular, bullous, and flechtanulous forms, which may spread and become generalized.

Severe skin reactions due to sun exposure, purpura, burning sensation, polymorphic erythema, increased sweating, dermatitis (contact, exfoliative, bullous), Stevens-Johnson syndrome, skin necrosis.

Rarely, the gel may increase sensitivity to UV radiation (natural and artificial sunlight). Therefore, direct sunlight should be avoided on treated areas during treatment and for two weeks after its completion (this also applies to visits to solariums).

Systemic reactions.

With prolonged use of the gel and/or application in large amounts, as well as with incorrect use or accidental overdose, systemic adverse effects may occur.

Gastrointestinal tract: upper abdominal pain, nausea, vomiting, bloating, loss of appetite, heartburn, diarrhea, constipation, peptic ulcer, gastrointestinal bleeding.

Nervous system: headache, dizziness, drowsiness.

Immune system: hypersensitivity reactions, including skin redness, desquamation, rash, blisters, urticaria, local skin swelling, bronchospasm, episodes of shortness of breath, anaphylactic reactions, angioedema, asthma.

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

Urinary system: cases of exacerbation of renal failure, interstitial nephritis.

Elderly patients are more prone to developing adverse reactions when using NSAIDs.

Since the gel contains ethanol in its composition, frequent use may cause dryness and irritation of the skin.

The medicinal product contains methylparahydroxybenzoate (E 218) and propylparahydroxybenzoate (E 216), which may cause allergic reactions (possibly delayed).

If adverse effects occur, the use of the gel must be discontinued and the skin surface thoroughly rinsed with running water.

Shelf life: 2 years.

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

Storage conditions.

Store at a temperature not exceeding 25 °C. Do not freeze.

Keep out of reach of children.

Packaging.

30 g or 50 g in aluminum tubes; 1 tube per cardboard box.

Prescription category.

By prescription.

Manufacturer.

JSC "Grindeks".

Manufacturer's address and location of its operations.

Krustpils St., 53, Riga, LV-1057, Latvia.

Applicant.

JSC "Grindeks".

Applicant's address.

Krustpils St., 53, Riga, LV-1057, Latvia.

Tel./fax: +371 67083205/+371 67083505.

E-mail: [email protected]

INSTRUCTION

for medical use of the medicinal product

VALUSAL®

(VALUSAL)

Composition:

Active substance: ketoprofen;

1 g of gel contains 25 mg of ketoprofen;

Excipients: ethanol 96%, carbomer, diethanolamine, lavender oil, methylparahydroxybenzoate (E 218), orange oil, propylparahydroxybenzoate (E 216), purified water.

Pharmaceutical form. Gel.

Main physicochemical properties: transparent or slightly cloudy, colorless or with a slight yellowish tint gel, with a specific odor.

Pharmacotherapeutic group.

Non-steroidal anti-inflammatory drugs for topical use.

ATC code M02A A10.

Pharmacological properties.

Pharmacodynamics.

Ketoprofen belongs to the group of non-steroidal anti-inflammatory drugs (NSAIDs) with pronounced analgesic action. The mechanism of action of the drug is based on reducing the synthesis of prostaglandins by inhibiting the activity of cyclooxygenases (COX-1 and COX-2). Ketoprofen stabilizes lysosomal membranes, suppresses leukotriene synthesis, and exhibits anti-bradykinin activity. It reduces pain and edema caused by inflammation.

Pharmacokinetics.

With repeated topical application of ketoprofen (e.g., 375 mg of ketoprofen), plasma concentration is approximately 100 times lower than with single oral administration of 150 mg of ketoprofen.

Ketoprofen is metabolized into acyl glucuronides and is mainly excreted in urine. The elimination half-life of ketoprofen after repeated gel application averages 17 hours, and bioavailability is approximately 5%.

Clinical characteristics.

Indications.

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

Contraindications.

• Hypersensitivity to ketoprofen or to excipients of the medicinal product, salicylates, and other NSAIDs.
• Known hypersensitivity reactions, e.g., symptoms of bronchial asthma, allergic rhinitis, or urticaria after administration of ketoprofen, other NSAIDs, salicylates (e.g., acetylsalicylic acid), fenofibrates, or tiaprofenic acid.
• Any history of photosensitization reactions.
• History of skin allergy symptoms that occurred during application of ketoprofen, excipients of the drug, fenofibrate, tiaprofenic acid, UV blockers, or perfumes.
• Exposure to sunlight (even on cloudy days), including indirect sunlight or solarium radiation, throughout the entire treatment period and for two weeks after discontinuation of the drug.
• Exacerbation of gastric or duodenal ulcer; history of gastrointestinal bleeding, chronic dyspepsia (discomfort and pain in the upper abdomen).
• Skin injuries, weeping dermatoses, rashes, skin trauma, irritations, itching, skin infections, acne, burns. The gel must not be applied to damaged skin (eczema, dermatoses, open or infected wounds).
• Do not use under occlusive dressings.
• Third trimester of pregnancy.
• Use in children.

Interaction with other medicinal products and other types of interactions.

Since plasma concentration of ketoprofen after topical application is very low, symptoms of interaction with other drugs (similar to those with systemic administration) are possible only with frequent and prolonged use:

• with methotrexate, cardiac glycosides, lithium salts, cyclosporine – increased toxicity due to reduced excretion;
• with anticoagulants, antithrombotic agents, acetylsalicylic acid or other NSAIDs, glucocorticoids, oral hypoglycemic agents, phenytoin – enhanced effects of the above-mentioned drugs; simultaneous use with other topical forms (creams, gels) containing ketoprofen or other NSAIDs is not recommended;
• with antihypertensive agents, diuretics, mifepristone – reduced efficacy of the above-mentioned drugs. At least 8 days must pass between mifepristone treatment course and initiation of ketoprofen therapy.

Simultaneous use of acetylsalicylic acid and ketoprofen reduces ketoprofen binding to plasma proteins.

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

Monitoring is recommended for patients who are simultaneously taking coumarins.

Special precautions.

Ketoprofen in gel form is intended only for topical use. If a dose is missed, do not double the dose at the next application.

Avoid contact of the gel with mucous membranes, areas around the eyes, and eyes. Hands should be washed after application, except when the gel is applied to the hands.

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

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

The drug should be used with caution in patients with impaired kidney or liver function, cardiovascular disease, severe renal insufficiency, bronchial asthma, or severe uncompensated heart failure. Patients with asthma combined with chronic rhinitis, sinusitis, or nasal polyps have a higher risk of allergy to aspirin or NSAIDs than the general population.

There have been reports of isolated cases of systemic adverse reactions associated with kidney damage. Topical application of large amounts of the drug may lead to such systemic effects as hypersensitivity and asthma.

Do not exceed the recommended amount of gel or duration of treatment, as the risk of contact dermatitis and photosensitivity reactions increases over time.

The drug should not be applied to large skin areas or under occlusive dressings.

During treatment and for two weeks after treatment, to reduce the risk of photosensitization, areas of skin treated with the gel must be protected from sunlight (even on cloudy days) and UV radiation in solariums. Treatment should be immediately discontinued if any skin reactions occur, including skin reactions after simultaneous use with substances containing octocrylene (an excipient found in some cosmetic and hygiene products such as shampoos, after-shave gels, shower gels, creams, lipsticks, anti-aging creams, makeup removers, hair lacquers, to prevent their photodegradation).

Use during pregnancy or breastfeeding.

In the first and second trimesters of pregnancy, the medicinal product should be used only after careful assessment of the benefit-risk ratio for the mother and potential risk to the fetus.

In the third trimester of pregnancy, prostaglandin synthesis inhibitors, including ketoprofen, may exhibit cardiopulmonary and renal toxicity in the fetus. Also, prostaglandin synthesis inhibitors may prolong bleeding time in both mother and child; therefore, the gel is contraindicated in the third trimester of pregnancy.

During breastfeeding, the gel is not recommended. Breastfeeding should be discontinued during treatment with ketoprofen.

Ability to affect reaction speed when driving or operating machinery.

No data available.

Method of administration and dosage.

For topical use.

Adults: apply a small amount of gel (3–5 cm) 2–3 times daily to the skin of the affected area and gently rub in. The skin at the painful site must be intact. The amount of gel applied depends on the size of the affected body area. The daily dose should not exceed 15 g (7.5 g corresponds to 14 cm of gel). Use the gel in short treatment courses. The duration of treatment depends on the nature of the disease and severity and is determined individually by the physician; usually, the treatment course lasts 1–10 days.

The treated area must not be covered with a bandage. Clothing in contact with the treated area should not cause discomfort to the patient. 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. Hands should be washed after applying the gel, except when the gel is applied to the hands. If prolonged rubbing into the skin is necessary, protective gloves should be used.

Elderly patients: No data indicating that elderly patients require different dosing.

Children: The gel must not be used in children due to insufficient data on the use of the medicinal product in this age group.

Overdose.

With topical application, the bioavailability of ketoprofen is low, making overdose unlikely.

With excessive topical doses, skin irritation, erythema, itching, or worsening of other adverse reactions may occur. If too much gel has been applied, the skin should be washed with water.

With incorrect use or accidental overdose, systemic adverse effects may occur.

In case of accidental oral ingestion, the drug may cause drowsiness, nausea, vomiting, dizziness, epigastric pain, bradypnea. High doses of ketoprofen with systemic administration may cause respiratory depression, coma, convulsions, gastrointestinal bleeding, acute renal failure, and increased or decreased blood pressure.

There is no specific antidote; symptomatic treatment with supportive care for vital functions is recommended. Gastric lavage and activated charcoal (the first dose should be administered with sorbitol) are recommended if less than 1 hour has passed since the overdose.

Adverse reactions.

Local reactions.

Local skin reactions may occur, which may spread beyond the area treated with the gel; in isolated cases, they may progress to severe reactions and spread throughout the entire body.

Skin and subcutaneous tissues: erythema, intense itching, burning sensation, eczema, including vesicular, bullous, and flechtanulous forms, which may spread and become generalized.

Severe skin reactions due to sun exposure, purpura, burning sensation, polymorphic erythema, increased sweating, dermatitis (contact, exfoliative, bullous), Stevens-Johnson syndrome, skin necrosis.

Rarely, the gel may increase sensitivity to UV radiation (natural and artificial sunlight). Therefore, direct sunlight should be avoided on treated areas during treatment and for two weeks after its completion (this also applies to visits to solariums).

Systemic reactions.

With prolonged use of the gel and/or application in large amounts, as well as with incorrect use or accidental overdose, systemic adverse effects may occur.

Gastrointestinal tract: upper abdominal pain, nausea, vomiting, bloating, loss of appetite, heartburn, diarrhea, constipation, peptic ulcer, gastrointestinal bleeding.

Nervous system: headache, dizziness, drowsiness.

Immune system: hypersensitivity reactions, including skin redness, desquamation, rash, blisters, urticaria, local skin swelling, bronchospasm, episodes of shortness of breath, anaphylactic reactions, angioedema, asthma.

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

Urinary system: cases of exacerbation of renal failure, interstitial nephritis.

Elderly patients are more prone to developing adverse reactions when using NSAIDs.

Since the gel contains ethanol in its composition, frequent use may cause dryness and irritation of the skin.

The medicinal product contains methylparahydroxybenzoate (E 218) and propylparahydroxybenzoate (E 216), which may cause allergic reactions (possibly delayed).

If adverse effects occur, the use of the gel must be discontinued and the skin surface thoroughly rinsed with running water.

Shelf life: 2 years.

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

Storage conditions.

Store at a temperature not exceeding 25 °C. Do not freeze.

Keep out of reach of children.

Packaging.

30 g or 50 g in aluminum tubes; 1 tube per cardboard box.

Prescription category.

By prescription.

Manufacturer.

JSC "Grindeks".

Manufacturer's address and location of its operations.

Krustpils St., 53, Riga, LV-1057, Latvia.

Applicant.

JSC "Grindeks".

Applicant's address.

Krustpils St., 53, Riga, LV-1057, Latvia.

Tel./fax: +371 67083205/+371 67083505.

E-mail: [email protected]

INSTRUCTION

for medical use of the medicinal product

VALUSAL®

(VALUSAL)

Composition:

Active ingredient: ketoprofen;

1 g of gel contains 25 mg of ketoprofen;

Inactive ingredients: ethanol 96 %, carbomer, diethanolamine, lavender oil, methylparahydroxybenzoate (E 218), orange oil, propylparahydroxybenzoate (E 216), purified water.

Pharmaceutical form. Gel.

Main physico-chemical properties: transparent or slightly opalescent, colourless or slightly yellowish gel with a characteristic odour.

Pharmacotherapeutic group.

Non-steroidal anti-inflammatory drugs for topical use.

ATC code M02A A10.

Pharmacological properties.

Pharmacodynamics.

Ketoprofen belongs to the group of nonsteroidal anti-inflammatory drugs (NSAIDs) with pronounced analgesic effect. The mechanism of action of the drug is based on reducing the synthesis of prostaglandins by inhibiting the activity of cyclooxygenases (COX-1 and COX-2). Ketoprofen stabilizes lysosomal membranes, suppresses the synthesis of leukotrienes, and exhibits anti-bradykinin activity. It reduces pain and swelling caused by inflammation.

Pharmacokinetics.

With repeated topical application of ketoprofen (e.g., 375 mg of ketoprofen), the plasma concentration is approximately 100 times lower than that achieved after a single oral dose of 150 mg of ketoprofen.

Ketoprofen is metabolized to acylglucuronides and is primarily excreted in the urine. The elimination half-life of ketoprofen after repeated gel application averages 17 hours, and bioavailability is approximately 5%.

Clinical characteristics.

Indications.

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

Contraindications.

• Hypersensitivity to ketoprofen or to excipients of the medicinal product, salicylates, or other NSAIDs.
• Known hypersensitivity reactions, such as bronchial asthma, allergic rhinitis, or urticaria following administration of ketoprofen, other NSAIDs, salicylates (e.g., acetylsalicylic acid), fenofibrate, or tiaprofenic acid.
• History of photosensitization reactions.
• History of skin allergy symptoms occurring during use of ketoprofen, excipients of the drug, fenofibrate, tiaprofenic acid, UV blockers, or perfumed products.
• Exposure to sunlight (even on cloudy days), including indirect sunlight or tanning bed radiation, during the entire treatment period and for at least 2 weeks after discontinuation of the drug.
• Acute exacerbation of gastric or duodenal ulcer; history of gastrointestinal bleeding, chronic dyspepsia (discomfort and pain in the upper abdomen).
• Skin lesions, exuding dermatoses, rashes, skin trauma, irritation, pruritus, skin infections, acne, burns. The gel must not be applied to damaged skin (eczema, dermatoses, open or infected wounds).
• Do not use under occlusive dressings.
• Third trimester of pregnancy.
• Use in children.

Interaction with other medicinal products and other forms of interaction.

Since plasma concentrations of ketoprofen are very low following topical application, symptoms of interaction with other drugs (similar to those observed with systemic administration) are possible only with frequent and prolonged use:

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

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

Concomitant use of probenecid and ketoprofen results in decreased clearance of ketoprofen and reduced extent of its protein binding.

Patients receiving coumarins should be monitored closely.

Special precautions for use

Ketoprofen in the form of a gel is intended for topical use only. If a dose is missed, do not double the dose at the next application.

Avoid contact of the gel with mucous membranes, areas around the eyes, and eyes. Hands must be washed after applying the medication.

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

The medicinal product should be used with caution and under physician supervision in patients receiving anticoagulants, diuretics, or lithium salts.

The product should be used with caution in patients with impaired renal or hepatic function, cardiovascular disease, severe renal insufficiency, bronchial asthma, and also in patients with severe uncompensated heart failure. Patients with asthma associated with chronic rhinitis, sinusitis, or nasal polyps have a higher risk of developing hypersensitivity to aspirin or NSAIDs compared to the general population.

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 such systemic effects as hypersensitivity and asthma.

Do not exceed the recommended amount of gel or duration of treatment, as the risk of developing contact dermatitis and photosensitivity reactions increases over time.

The product should not be applied over large areas of skin or under occlusive dressings.

During treatment and for 2 weeks after treatment, areas of skin treated with the gel should be protected from sunlight (even on cloudy days) and from UV radiation in tanning beds to reduce the risk of photosensitization. Treatment should be discontinued immediately if any skin reactions occur, including skin reactions following concomitant use with substances containing octocrylene (an excipient found in some cosmetic and hygiene products such as shampoos, after-shave gels, shower gels, creams, lipsticks, anti-aging creams, makeup removers, hair sprays) used to prevent their photodegradation.

Use during pregnancy or breastfeeding

During the first and second trimesters of pregnancy, the medicinal product should be used only after careful assessment of the benefit-risk ratio for the mother and potential risk to the fetus.

During the third trimester of pregnancy, prostaglandin synthesis inhibitors, including ketoprofen, may cause cardiopulmonary and renal toxicity in the fetus. Prostaglandin synthesis inhibitors may also prolong bleeding time in both mother and child. Therefore, the gel is contraindicated during the third trimester of pregnancy.

During breastfeeding, use of the gel is not recommended. Breastfeeding should be discontinued during treatment with ketoprofen.

Ability to influence reaction rate while driving or operating machinery

No data available.

Method of Administration and Dosage

For external use only.

Adults: Apply a small amount of gel (3–5 cm) to the affected area of skin 2–3 times daily and gently rub in. The skin at the painful site must be intact. The quantity of gel applied depends on the size of the affected body area.

The daily dose should not exceed 15 g (7.5 g corresponds to 14 cm of gel). The gel should be used in short treatment courses. The duration of treatment depends on the nature and severity of the condition and is determined individually by a physician; typically, the treatment course lasts 1–10 days.

The affected skin area should not be covered with a bandage. Clothing in contact with the treated area should not cause discomfort to the patient. 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. Hands should be washed after applying the gel, except when the gel is applied directly to the hands. In case of prolonged rubbing into the skin, protective gloves should be used.

Elderly patients: There are no data indicating that elderly patients require a different dosage.

Children: The gel should not be used in children due to insufficient data on the use of the medicinal product in this age group.

Overdose

When applied topically, the bioavailability of ketoprofen is low, making overdose unlikely.

With topical application of very large doses, skin irritation, erythema, pruritus, or exacerbation of other adverse reactions may occur. If an excessive amount of gel has been applied to the skin, it should be washed off with water.

Incorrect use or accidental overdose may lead to systemic adverse effects.

In case of accidental oral ingestion of ketoprofen, symptoms such as drowsiness, nausea, vomiting, dizziness, epigastric pain, and bradypnea may occur. High doses of ketoprofen with systemic use may cause respiratory depression, coma, convulsions, gastrointestinal bleeding, acute renal failure, and increased or decreased arterial blood pressure.

There is no specific antidote; symptomatic treatment together with supportive measures to maintain vital functions is recommended. Gastric lavage and administration of activated charcoal (the first dose should be given with sorbitol) are recommended if less than 1 hour has passed since the overdose.

Adverse Reactions

Local Reactions

Local skin reactions may occur, which may spread beyond the area treated with the gel; in isolated cases, they may progress to severe reactions and become generalized.

Skin and subcutaneous tissues: erythema, intense pruritus, burning sensation, eczema (including vesicular, bullous, and flektenulose forms), which may spread and become generalized.

Severe skin reactions due to sun exposure, purpura, burning sensation, polymorphous erythema, increased sweating, dermatitis (contact, exfoliative, bullous), Stevens-Johnson syndrome, skin necrosis.

Rarely, the gel may increase sensitivity to UV radiation (natural and artificial sunlight). Therefore, direct sunlight should be avoided on treated areas during treatment and for two weeks after its completion (this also applies to visits to solariums).

Systemic Reactions

With prolonged use of the gel and/or application in large amounts, as well as with incorrect use or accidental overdose, systemic adverse effects may occur.

Gastrointestinal tract: upper abdominal pain, nausea, vomiting, bloating, loss of appetite, heartburn, diarrhea, constipation, peptic ulcer, gastrointestinal bleeding.

Nervous system: headache, dizziness, drowsiness.

Immune system: hypersensitivity reactions, including skin redness, desquamation, rash, blisters, urticaria, local skin swelling, bronchospasm, episodes of dyspnea, anaphylactic reactions, angioneurotic edema, asthma.

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

Urinary system: cases of exacerbation of renal failure, interstitial nephritis.

Elderly patients are more prone to adverse reactions when using NSAIDs.

Since the gel contains ethanol, frequent use may cause dryness and irritation of the skin.

The medicinal product contains methylparahydroxybenzoate (E 218) and propylparahydroxybenzoate (E 216), which may cause allergic reactions (possibly delayed).

In case of adverse reactions, the use of the gel must be discontinued and the skin surface thoroughly rinsed with running water.

Shelf life: 2 years.

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

Storage Conditions

Store at a temperature not exceeding 25 °C. Do not freeze.

Keep out of reach of children.

Packaging

30 g or 50 g in aluminum tubes; one tube per cardboard box.

Prescription Category

Prescription only.

Manufacturer

JSC Tallinn Pharmaceutical Plant.

Manufacturer's address and location of operations:

Tondi 33, 11316 Tallinn, Estonia.

Marketing Authorization Holder

JSC "Grindeks".

Address of the Marketing Authorization Holder:

Krustpils St. 53, Riga, LV-1057, Latvia.

Tel./fax: +371 67083205 / +371 67083505.

E-mail: [email protected]

PACKAGE LEAFLET

MEDICAL INSTRUCTIONS FOR THE MEDICINAL PRODUCT

VALUSAL®

(VALUSAL)

Composition:

Active substance: ketoprofenum;

1 g of gel contains 25 mg of ketoprofen;

Excipients: ethanol 96%, carbomer, diethanolamine, lavender oil, methylparahydroxybenzoate (E 218), orange oil, propylparahydroxybenzoate (E 216), purified water.

Pharmaceutical Form: Gel.

Main physicochemical properties: transparent or slightly cloudy, colorless or slightly yellowish gel with a specific odor.

Pharmacotherapeutic Group

Non-steroidal anti-inflammatory drugs for topical use.

ATC Code: M02AA10.

Pharmacological Properties

Pharmacodynamics

Ketoprofen belongs to the group of non-steroidal anti-inflammatory drugs (NSAIDs) with pronounced analgesic effects. The mechanism of action involves reduction of prostaglandin synthesis by inhibiting cyclooxygenase (COX-1 and COX-2) activity. Ketoprofen stabilizes lysosomal membranes, suppresses leukotriene synthesis, and exhibits anti-bradykinin activity. It reduces pain and swelling caused by inflammation.

Pharmacokinetics

With repeated topical application of ketoprofen (e.g., 375 mg ketoprofen), plasma concentration is approximately 100 times lower than after single oral administration of 150 mg ketoprofen.

Ketoprofen is metabolized into acylglucuronides and is primarily excreted in urine. The elimination half-life of ketoprofen after repeated gel application averages 17 hours, with bioavailability of approximately 5%.

Clinical Characteristics

Indications

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

Contraindications

• Hypersensitivity to ketoprofen or any of the excipients, salicylates, or other NSAIDs.
• Known hypersensitivity reactions, such as symptoms of bronchial asthma, allergic rhinitis, or urticaria following administration of ketoprofen, other NSAIDs, salicylates (e.g., acetylsalicylic acid), fenofibrates, or tiaprofenic acid.
• History of photosensitization reactions.
• History of skin allergy symptoms following use of ketoprofen, excipients of the product, fenofibrate, tiaprofenic acid, UV blockers, or perfumes.
• Exposure to sunlight (even on cloudy days), including indirect sunlight or solarium radiation, throughout the entire treatment period and for 2 weeks after discontinuation.
• Active peptic ulcer of the stomach or duodenum; history of gastrointestinal bleeding; chronic dyspepsia (discomfort and pain in the upper abdomen).
• Skin lesions, weeping dermatoses, rashes, skin injuries, irritations, itching, skin infections, acne, burns. The gel must not be applied to damaged skin (eczema, dermatoses, open or infected wounds).
• Do not use under occlusive dressings.
• Third trimester of pregnancy.
• Use in children.

Interaction with Other Medicinal Products and Other Forms of Interaction

Due to the very low plasma concentration of ketoprofen after topical application, systemic interaction symptoms (similar to those with systemic use) are possible only with frequent and prolonged use:

• With methotrexate, cardiac glycosides, lithium salts, cyclosporine – increased toxicity due to reduced excretion;
• With anticoagulants, antiplatelet agents, acetylsalicylic acid or other NSAIDs, glucocorticoids, oral hypoglycemic agents, phenytoin – enhanced effects of these drugs; concomitant use with other topical formulations (creams, gels) containing ketoprofen or other NSAIDs is not recommended;
• With antihypertensives, diuretics, mifepristone – reduced efficacy of these drugs. At least 8 days must elapse between mifepristone treatment and initiation of ketoprofen therapy.

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

Concomitant use of probenecid and ketoprofen reduces ketoprofen clearance and protein binding.

Patients receiving coumarins should be monitored.

Special Precautions

Ketoprofen in gel form is intended for external use only. If a dose is missed, do not double the next dose.

Avoid contact with mucous membranes, areas around the eyes, and eyes. Hands should be washed after application, unless the gel is applied to the hands.

Do not apply to damaged skin (e.g., eczema, acne, infection, or open wounds).

Use with caution and under physician supervision in patients taking anticoagulants, diuretics, or lithium salts.

Use with caution in patients with impaired kidney or liver function, cardiovascular disease, severe renal insufficiency, bronchial asthma, or severe uncompensated heart failure. Patients with asthma combined with chronic rhinitis, sinusitis, or nasal polyps have a higher risk of allergy to aspirin or NSAIDs than the general population.

There have been reports of rare cases of systemic adverse reactions involving kidney damage. Topical application of large amounts of the drug may lead to systemic effects such as hypersensitivity and asthma.

Do not exceed the recommended dose or duration of treatment, as the risk of contact dermatitis and photosensitivity reactions increases over time.

The product should not be applied to large skin areas or under occlusive dressings.

During treatment and for 2 weeks after, areas treated with the gel must be protected from sunlight (even on cloudy days) and UV radiation in solariums. Treatment must be stopped immediately if any skin reactions occur, including skin reactions after concomitant use with substances containing octocrylene (an excipient found in some cosmetic and hygiene products such as shampoos, shaving gels, shower gels, creams, lipsticks, anti-aging creams, makeup removers, hair sprays, and products to prevent photodegradation).

Use During Pregnancy or Breastfeeding

In the first and second trimesters of pregnancy, the medicinal product should be used only after careful assessment of the benefit-risk ratio for the mother and potential risk to the fetus.

In the third trimester of pregnancy, prostaglandin synthesis inhibitors, including ketoprofen, may cause cardiopulmonary and renal toxicity in the fetus. These inhibitors may also prolong bleeding time in both mother and child; therefore, the gel is contraindicated in the third trimester of pregnancy.

Use during breastfeeding is not recommended. Breastfeeding should be discontinued during treatment with ketoprofen.

Effect on Ability to Drive or Operate Machinery

No data available.

Method of Administration and Dosage

For external use only.

Adults: Apply a small amount of gel (3–5 cm) 2–3 times daily to the affected area and gently rub in. The skin at the site of application must be intact. The amount of gel applied depends on the size of the affected area. The daily dose should not exceed 15 g (7.5 g corresponds to 14 cm of gel). Use in short treatment courses. Duration of treatment depends on the nature and severity of the condition and is determined individually by the physician; typically, treatment lasts 1–10 days.

The treated area should not be covered with a bandage. Clothing in contact with the treated area should not cause discomfort. There is no need to apply a dry dressing, as the gel is well absorbed, odorless, dye-free, and does not leave greasy stains or soil clothing. Hands should be washed after application, unless the gel is applied to the hands. Protective gloves are recommended if prolonged rubbing into the skin is required.

Elderly patients: No data indicate that elderly patients require different dosing.

Children: The gel should not be used in children due to insufficient data on safety and efficacy in this age group.

Overdose

Due to low systemic bioavailability after topical application, overdose is unlikely.

Excessive topical doses may cause skin irritation, erythema, itching, or worsening of other adverse reactions. If excessive gel has been applied, the skin should be washed with water.

Incorrect use or accidental overdose may lead to systemic adverse effects.

Accidental oral ingestion may cause drowsiness, nausea, vomiting, dizziness, epigastric pain, and bradypnea. High systemic doses of ketoprofen may cause respiratory depression, coma, convulsions, gastrointestinal bleeding, acute renal failure, and increased or decreased blood pressure.

There is no specific antidote. Symptomatic treatment with supportive care of vital functions is recommended. Gastric lavage and activated charcoal (the first dose should be administered with sorbitol) are recommended if less than 1 hour has passed since ingestion.

Adverse Reactions

Local Reactions

Local skin reactions may occur, which may extend beyond the treated area; in rare cases, they may become severe and generalized.

Skin and subcutaneous tissues: erythema, intense pruritus, burning sensation, eczema (including vesicular, bullous, and flektenulose forms), which may spread and become generalized.

Severe skin reactions due to sun exposure, purpura, burning sensation, polymorphous erythema, increased sweating, dermatitis (contact, exfoliative, bullous), Stevens-Johnson syndrome, skin necrosis.

Rarely, the gel may increase sensitivity to UV radiation (natural and artificial sunlight). Therefore, direct sunlight should be avoided on treated areas during treatment and for two weeks after its completion (this also applies to visits to solariums).

Systemic Reactions

With prolonged use of the gel and/or application in large amounts, as well as with incorrect use or accidental overdose, systemic adverse effects may occur.

Gastrointestinal tract: upper abdominal pain, nausea, vomiting, bloating, loss of appetite, heartburn, diarrhea, constipation, peptic ulcer, gastrointestinal bleeding.

Nervous system: headache, dizziness, drowsiness.

Immune system: hypersensitivity reactions, including skin redness, desquamation, rash, blisters, urticaria, local skin swelling, bronchospasm, episodes of dyspnea, anaphylactic reactions, angioedema, asthma.

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

Urinary system: cases of exacerbation of renal failure, interstitial nephritis.

Elderly patients are more prone to adverse reactions when using NSAIDs.

Since the gel contains ethanol, frequent use may cause dryness and skin irritation.

The medicinal product contains methylparahydroxybenzoate (E 218) and propylparahydroxybenzoate (E 216), which may cause allergic reactions (possibly delayed).

In case of adverse reactions, the use of the gel must be discontinued and the skin surface thoroughly rinsed with running water.

Shelf life: 2 years.

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

Storage Conditions

Store at a temperature not exceeding 25 °C. Do not freeze.

Keep out of reach of children.

Packaging

30 g or 50 g in aluminum tubes; one tube per cardboard box.

Prescription Category

Prescription only.

Manufacturer

JSC Tallinn Pharmaceutical Plant.

Manufacturer's address and location of operations:

Tondi 33, 11316 Tallinn, Estonia.

Marketing Authorization Holder

JSC "Grindeks".

Address of the Marketing Authorization Holder:

Krustpils St. 53, Riga, LV-1057, Latvia.

Tel./fax: +371 67083205 / +371 67083505.

E-mail: [email protected]