Clobesil

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Clobesil (CLOBESIL)

Composition:

Active ingredient: diclofenac;

1 g of gel contains 50 mg of sodium diclofenac;

Excipients: benzyl alcohol, purified water, diethylene glycol monoethyl ether, 96% ethanol, propylene glycol, hydroxyethylcellulose.

Pharmaceutical form. Gel.

Main physicochemical properties: colorless or slightly pink homogeneous gel.

Pharmacotherapeutic group.

Agents used locally for joint and muscular pain. Topical non-steroidal anti-inflammatory drugs. Diclofenac. ATC code M02A A15.

Pharmacological properties.

Pharmacodynamics.

Clobesil is a non-steroidal anti-inflammatory agent for topical use from the group of phenylacetic acid derivatives. The drug exerts pronounced local anti-rheumatic, analgesic, and anti-inflammatory effects, which are due to inhibition of prostaglandin synthesis—mediators of pain and inflammation.

In inflammation caused by injuries or rheumatic diseases, Clobesil leads to reduction of pain, tissue swelling, and shortening of the recovery period for functions of damaged joints, ligaments, tendons, and muscles.

Pharmacokinetics.

Sodium diclofenac is slowly and partially absorbed through the skin surface. The amount of diclofenac absorbed through the skin is proportional to the application area and depends on both the total applied dose of the drug and the degree of skin hydration. Maximum plasma concentration is observed within 6–9 hours. After oral administration, maximum plasma concentration is reached approximately within 1–2 hours. The mean duration of the active substance in systemic circulation is about 9 hours, which is significantly longer compared to 1–2 hours after oral administration.

Diclofenac accumulates in the skin, which acts as a reservoir, allowing gradual release of the substance into adjacent tissues. From there, diclofenac predominantly penetrates into deeper inflamed tissues, such as joints, where it continues to exert its effect and is found in concentrations up to 20 times higher than in plasma.

Metabolism and elimination of the drug after topical application are similar to those following systemic administration. Diclofenac and its metabolites are mainly excreted via urine. Total systemic plasma clearance of diclofenac is 263 ± 56 ml/min, and the terminal half-life is on average 1–3 hours. Diclofenac is 99% bound to plasma proteins. Following rapid hepatic metabolism (hydroxylation and conjugation with glucuronic acid), about two-thirds of the substance is excreted by the kidneys and one-third via bile.

In renal or hepatic insufficiency, metabolism and elimination of diclofenac from the body remain unchanged.

Clinical characteristics.

Indications.

Local treatment of pain and inflammation of joints, muscles, ligaments, and tendons of rheumatic or traumatic origin.

Contraindications.

Hypersensitivity to diclofenac or to other nonsteroidal anti-inflammatory drugs, or to any component of the medicinal product. History of bronchial asthma attacks, urticaria, acute rhinitis, nasal polyps, or angioedema induced by acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs. Third trimester of pregnancy.

Children.

Interaction with other medicinal products and other forms of interactions.

Since systemic absorption of diclofenac following topical application of the drug is very low, the occurrence of interactions is unlikely.

Special precautions for use

The drug should be used with caution in combination with oral nonsteroidal anti-inflammatory agents.

The likelihood of systemic adverse effects with topical application of diclofenac is low compared to oral forms; however, it cannot be completely excluded when the drug is applied over relatively large skin areas for prolonged periods.

Klobesil gel should be applied only to intact skin areas, avoiding contact with inflamed, wounded, or infected skin. Contact of the drug with eyes and mucous membranes should be avoided. The drug must not be used internally.

If any skin rash develops, treatment with the drug should be discontinued. Application under an airtight occlusive dressing is not recommended, but use under a non-occlusive dressing is acceptable. In cases of ligament sprain, the affected area may be bandaged with a wrap.

Do not apply to open wounds or infected skin, or to skin areas affected by eczema, or to mucous membranes.

Due to the possibility of photosensitivity reactions, exposure to direct sunlight and use of solariums should be avoided during treatment and for 2 weeks after discontinuation of treatment.

Klobesil 5% gel contains propylene glycol, which may cause skin irritation.

Use during pregnancy or breastfeeding

Pregnancy

There are no clinical data on the use of Klobesil during pregnancy. Although systemic effects are lower than with oral administration, it is unknown whether the systemic exposure to Klobesil achieved after topical application could be harmful to the embryo/fetus. During the first and second trimesters of pregnancy, Klobesil should not be used 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 synthesis inhibitors, including Klobesil, may cause cardiopulmonary and renal toxicity in the fetus. At late stages of pregnancy, prolonged bleeding may occur in both mother and child, and labor may be delayed. Therefore, Klobesil is contraindicated during the last trimester of pregnancy (see section "Contraindications").

It is unknown whether diclofenac is excreted in breast milk following topical application. Therefore, use of Klobesil during breastfeeding is permitted only if the expected benefit, in the physician's opinion, outweighs the potential risk to the infant. If there are strong reasons for using the drug during breastfeeding, the gel should not be applied to the breasts or large skin areas, and should not be used in larger amounts or for longer durations than recommended.

Fertility
There are no available data on the effect of topically applied diclofenac on human fertility.

Ability to affect reaction speed when driving or operating machinery
No effect.

Method of Administration and Dosage

Apply Clobesil 3–4 times daily, gently rubbing it into the skin. The amount of the drug used depends on the size of the affected area (for example, 2–4 g of gel, corresponding in volume to the size of a cherry or a walnut, is sufficient for application to an area of 400–800 cm²).

After applying the drug, hands should be washed unless the hands themselves are the area being treated.

The duration of therapy depends on the nature of the disease and the effectiveness of treatment.

The drug should not be used for longer than 14 consecutive days.

If the drug is used without a doctor's prescription, it is necessary to consult a physician if the patient's condition does not improve or worsens after 7 days of treatment.

Elderly patients (aged 65 years and older). There is no reason to believe that elderly patients require a special dose adjustment or are at risk of experiencing adverse reactions different from those in other patients.

Patients with renal impairment. There is no reason to believe that patients with renal impairment require a special dose adjustment.

Patients with hepatic impairment. There is no reason to believe that patients with hepatic impairment require a special dose adjustment.

Children.

Dosage recommendations and therapeutic indications for the use of Clobesil in children are not available.

Overdose.

Overdose is unlikely due to the low systemic absorption of diclofenac following topical application. However, in case of accidental ingestion, it should be noted that one 45 g tube of the drug contains the equivalent of 2,250 mg of sodium diclofenac, which may lead to the development of systemic adverse reactions.

In case of accidental ingestion, the stomach should be emptied immediately and an adsorbent administered. Symptomatic treatment and therapeutic measures appropriate for overdose with nonsteroidal anti-inflammatory drugs should be implemented.

Adverse reactions.

Clobexil is generally well tolerated. Adverse reactions include mild transient skin reactions at the application site. Allergic reactions may occur rarely.

The assessment of adverse reactions is presented according to frequency of occurrence: 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).

Infections and infestations: very rare – pustular eruptions.

Skin and subcutaneous tissue disorders: uncommon – rash, pruritus, erythema, eczema, exanthema, burning sensation, edema, vesicle formation, papules, pustules, desquamation, dry skin, dermatitis (including contact dermatitis); rare – bullous dermatitis; very rare – photosensitivity reactions, generalized skin eruptions, skin burning sensation.

Respiratory system disorders: very rare – bronchial asthma.

Gastrointestinal disorders: adverse reactions occur very rarely following topical application of preparations containing diclofenac.

When the gel is used in high doses or applied to large areas of skin, systemic adverse reactions cannot be excluded, as well as hypersensitivity reactions such as angioedema and dyspnea.

Shelf life. 3 years.

Storage conditions.

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

Keep out of reach of children.

Packaging.

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

Availability. Over-the-counter.

Manufacturer.

ANTIBIOTICE SA

ANTIBIOTICE SA

Manufacturer's address and location of business activity.

1, Valea Lupului Street, Iasi 707410, Romania