Relief® pro

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT RELIEF® PRO (RELIEF®PRO)

Composition:

Active substances: 1 g of rectal cream contains 1 mg micronized fluocortolone pivalate and 20 mg lidocaine hydrochloride monohydrate;

Excipients: polysorbate 60, sorbitan stearate, cetostearyl alcohol, mineral oil, white soft paraffin, disodium edetate, sodium dihydrogen phosphate dihydrate, sodium hydrogen phosphate dodecahydrate, benzyl alcohol, purified water.

Pharmaceutical form. Rectal cream.

Main physicochemical characteristics: white opaque cream.

Pharmacotherapeutic group. Agents for treatment of haemorrhoids and anal fissures for topical use. Corticosteroids. Fluocortolone. ATC code C05AA08.

Pharmacological Properties

Pharmacodynamics

Fluocortolone pivalate suppresses inflammatory and allergic skin reactions and also relieves subjective symptoms such as itching, burning sensation, and pain; it reduces capillary dilation, interstitial cell edema, tissue infiltration, and inhibits capillary proliferation.

Lidocaine hydrochloride is a standard local anesthetic agent that has been used in medical practice for many years. Due to its analgesic effect, it is effective when administered in suppositories and ointments intended for the treatment of disorders associated with hemorrhoidal pathology. Pain and itching reduction are related to the inhibition of afferent nerve impulses.

Pharmacokinetics

After application of the cream in the rectal area, maximum systemic absorption in healthy male volunteers was 15% of the dose of fluocortolone pivalate and 30% of the dose of lidocaine hydrochloride (active substances labeled with a radioactive isotope).

Clinical characteristics.

Indications.

For symptomatic treatment of pain and inflammation in cases of:

• haemorrhoids;
• proctitis;
• perianal eczema.

Contraindications.

The use of Relief**®** Pro is contraindicated in local infections at the site of application, as well as in the presence of clear symptoms of the following pathological conditions in the relevant areas:

• specific skin lesions (syphilis, tuberculosis);
• varicella;
• post-vaccination reactions;
• genital herpes;
• smallpox;
• other viral infections;
• primary bacterial or fungal infections;
• secondary skin infections in the absence of appropriate therapy.

Patients with hypersensitivity to other local anesthetics of the amide type (e.g., bupivacaine, etidocaine, mepivacaine, and prilocaine).

Relief**®** Pro should not be used in cases of hypersensitivity to the active substances or to any of the excipients, for example, to cetostearyl alcohol.

Special precautions.

When using the rectal cream Relief**®** Pro in the genital area or around the anal opening, excipients such as soft white paraffin and mineral oil may reduce the strength of latex condoms and thus impair their reliability.

In case of fungal infections, additional specific antifungal therapy is required.

Contact of the cream with the eyes should be avoided. Hands should be thoroughly washed after application.

Cetostearyl alcohol may cause local skin reactions (contact dermatitis).

The use of topical preparations, especially over prolonged periods, may lead to sensitization phenomena. In such cases, the use of these preparations should be discontinued and appropriate treatment initiated. When topical preparations are applied over large areas of the body, on damaged skin, or under occlusive dressings, corticosteroids may be absorbed in amounts sufficient to cause systemic adverse effects. Do not use under occlusive dressings in the perineal area. Adrenal suppression may occur even without occlusion. Local application of corticosteroids in high doses may result in systemic absorption of corticosteroid amounts sufficient to cause systemic effects. Scientific literature reports cases of cataract development in patients using corticosteroids over a prolonged period; therefore, the potential role of corticosteroids in cataract development should be considered to exclude systemic effects of corticosteroids.

Use with caution in acute illnesses, debilitated patients, elderly patients, and in patients with severe cardiac, renal, or hepatic insufficiency.

Interaction with other medicinal products and other forms of interaction.

Interaction studies have not been conducted. Patients taking antiarrhythmic drugs should use the rectal cream Relief**®** Pro with caution, as it contains lidocaine as the active ingredient.

Use with caution in patients taking other local anesthetics, as there may be an increased risk of adverse reactions; monoamine oxidase inhibitors enhance the local analgesic effect of lidocaine.

Concomitant use with CYP3A inhibitors, including cobicistat in tablet form, is considered to increase the risk of systemic adverse effects. Such combination should be avoided unless the benefit outweighs the risk of systemic adverse effects associated with corticosteroid use. When used concomitantly, the patient's condition should be monitored to ensure absence of systemic adverse effects related to corticosteroid use.

Special precautions for use.

Use during pregnancy or breastfeeding.

Data on the use of Rectal Cream Relief**®** Pro in pregnant women are insufficient. Animal studies with glucocorticoids have shown reproductive toxicity.

Some epidemiological studies suggest a possible increased risk of cleft palate in newborns whose mothers received systemic glucocorticoid therapy during the first trimester of pregnancy. Cleft palate ("wolf mouth") is a rare condition, and although systemic use of glucocorticoids is associated with teratogenic effects, their use can be considered a cause of this condition only if the incidence increases by one or two cases per 1000 women who received such treatment during pregnancy.

Data on the topical use of glucocorticoids for treating women during pregnancy are insufficient; however, the risk can be considered low, as glucocorticoids have very low systemic bioavailability when applied topically.

In general, topical preparations containing glucocorticoids should not be used during the first trimester of pregnancy.

When prescribing treatment for pregnant or breastfeeding women, a careful assessment of clinical indications for using Rectal Cream Relief**®** Pro, as well as the risk-benefit ratio, should be conducted. In particular, prolonged use of the medicinal product should be avoided.

Ability to influence reaction rate while driving or operating machinery. No effect.

Method of Administration and Dosage

Apply Rectal Cream Relief® Pro twice daily, in the morning and evening (approximately 1 gram per application). During the first few days of treatment, the medication may be used three times daily. After improvement, application once daily may be sufficient. It is recommended to apply Rectal Cream Relief® Pro after defecation. Prior to application, the anal area should be gently cleaned.

The total duration of treatment should not exceed 2 weeks.

Apply Rectal Cream Relief® Pro on the fingertip around the anal opening, gently overcoming the resistance of the sphincter. One dose applied on the fingertip corresponds to the amount obtained after a single squeezing from the tube and applied to the surface of an adult's index finger. If rectal cream Relief® Pro needs to be administered inside the rectum, screw the applicator onto the tube and insert the tip into the anal canal. A small amount of cream can also be administered by gently pressing the tube.

Do not use the applicator if it is damaged. Screw the applicator fully onto the tube. After each use, wipe the applicator surface with a paper towel, clean any residual cream from inside the applicator using cotton swabs, and wipe the applicator again with a paper towel. Rinse the applicator under warm water for 1 minute and dry it thoroughly with a paper towel.

Children. Not recommended for use in children due to lack of data on safety and efficacy.

Overdose.

Results of studies on potential acute toxicity associated with the active ingredients in Relief® Pro indicate no risk of symptoms related to acute toxicity following accidental overdose due to a single rectal administration of the medication.

In case of accidental ingestion of the medicinal product (if several grams of cream are swallowed), systemic symptoms caused by lidocaine hydrochloride are expected. Depending on the dose, these may manifest as severe cardiovascular disturbances (decreased blood pressure, excessive sweating, pallor, bradycardia, arrhythmia, cardiac depression, shock, or in particularly severe cases—cardiac arrest) or reactions related to central nervous system disturbances (headache, dizziness, blurred vision, diplopia, tinnitus, drowsiness, limb numbness, chills, restlessness, seizures, dyspnea, or in particularly severe cases—respiratory failure). Methemoglobinemia is possible.

Treatment in case of overdose includes careful monitoring of vital functions, supportive measures to maintain oxygen levels, and symptomatic treatment of central nervous system and cardiovascular disturbances, for example, administration of short-acting barbiturates, beta-sympathomimetics, and atropine. Dialysis does not provide sufficient effect.

Adverse reactions.

The incidence of adverse effects is based on the pooled data from clinical studies involving 661 patients.

Skin and subcutaneous tissue disorders, including allergic reactions:
Common: pain and burning sensation at the application site;
Uncommon: irritation at the application site.

With prolonged treatment using Relif**®** Pro cream (exceeding 4 weeks), there is a risk of developing local skin pathological conditions such as atrophy, striae, or telangiectasia.

Adverse reactions due to lidocaine hydrochloride: anaphylactic reactions. Systemic adverse reactions are unlikely because systemic absorption of lidocaine following topical application is minimal. Systemic adverse reactions associated with lidocaine are similar in presentation to those associated with amide-type local anesthetics.

Shelf life. 3 years.

After first opening, the storage period is 4 weeks.

Storage conditions.

Store out of reach of children at a temperature not exceeding 30 °C.

Packaging.

15 g or 30 g in a tube, 1 tube with an applicator in a cardboard box labeled in Ukrainian.

Availability category. Over-the-counter.

Manufacturer.

LEO Pharma Manufacturing Italy SRL /
LEO Pharma Manufacturing Italy SRL.

Manufacturer's address.

Via E. Schering, 21, 20054, Segrate (MI), Italy /
Via E. Schering, 21, 20054, Segrate (MI), Italy.

Marketing authorization holder.

Bayer Consumer Care AG /
Bayer Consumer Care AG.

Address of the marketing authorization holder.

Peter Merian-Strasse 84, 4052 Basel, Switzerland /
Peter Merian-Strasse 84, 4052 Basel, Switzerland.