Dermazin

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DERMAZIN (DERMAZIN®)

Composition:

Active substance: silver sulfadiazine;

1 g of cream contains silver sulfadiazine 10 mg;

Excipients: cetostearyl alcohol, hydrogenated peanut oil, polysorbate 60, propylene glycol, methylparaben (methylparahydroxybenzoate) (E 218), propylparaben (propylparahydroxybenzoate) (E 216), purified water.

Pharmaceutical form. Cream.

Main physicochemical properties: homogeneous white cream.

Pharmacotherapeutic group.

Antibacterial and chemotherapeutic agents used in dermatology. Sulfonamides. ATC code D06B A01.

Pharmacological properties.

Pharmacodynamics.

Dermazine is a topical chemotherapeutic agent with antimicrobial activity used for the treatment and prevention of wound infections, including burns.

Silver sulfadiazine dissociates at the wound surface in such a way as to provide slow and continuous release of silver ions. Silver ions bind to bacterial DNA, thereby inhibiting the growth and reproduction of bacterial cells, without affecting skin and subcutaneous tissue cells.

Dermazine has a broad spectrum of antibacterial activity, covering almost all microorganisms responsible for infections of burned and other wounded skin surfaces.

Minimum inhibitory concentration (MIC) of silver sulfadiazine in vitro for some important microorganisms:

For Herpes, Herella, Rhizopus nigricans, MIC ≤ 10 mcg/mL.

Dermazin penetrates necrotic tissues and exudate. This effect is very important considering that systemic antibiotics are ineffective against bacterial flora in necrotic tissues.

Pharmacokinetics.

With prolonged treatment of burn wounds over a large body surface area, the drug may be absorbed. Serum sulfonamide concentrations are proportional to the surface area of the burn wound and the amount of cream applied. Argiria (pigmentation caused by silver deposition) due to systemic absorption of silver is minimal.

Approximately 60% of absorbed sulfadiazine is excreted unchanged in urine, with a half-life of 10 hours. In patients with anuria, this half-life may increase up to 22 hours.

Clinical characteristics.

Indications.

Prevention of infection and treatment of infected burns, pressure ulcers, ulcers, superficial wounds with mild exudation, abrasions.

Prevention of infection during skin transplantation.

Contraindications.

Hypersensitivity to silver sulfadiazine, sulfonamides, or to any other ingredient of the medicinal product. Known hypersensitivity to peanuts or soy. Porphyria. Glucose-6-phosphate dehydrogenase deficiency (hemolysis may occur when applied to large surfaces). Purulent and burn wounds with abundant exudation (inappropriate). Premature infants, newborns, and children under 3 months of age (due to the risk of developing bilirubin encephalopathy).

Interaction with other medicinal products and other types of interactions.

Silver sulfadiazine may inactivate enzymatic wound debriding agents when used concomitantly.

Concomitant use of cimetidine may increase the incidence of leukopenia.

When treating large burns, serum concentrations of silver sulfadiazine may reach therapeutic levels; therefore, it should be considered that the effects of systemically administered drugs may be altered. Possible interactions with other agents typical for systemic sulfonamides: reduced effect of anticoagulants, oral antidiabetic agents, local anesthetics (procaine, benzocaine, tetracaine), and enhanced effect of phenytoin.

Special precautions for use

Avoid contact of the product with the eyes.

Dermazine cream should be used with caution:

• in patients with hypersensitivity to sulfonamides (due to the possibility of allergic reactions);
• in patients with congenital glucose-6-phosphate dehydrogenase deficiency (when treating minor superficial burns);
• in patients with impaired renal or hepatic function (cumulation may occur; such patients require monitoring of sulfonamide levels in blood serum).

Do not use in patients with porphyria (see section "Contraindications"). Local application of the cream may provoke the onset of porphyria.

Serious skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported during treatment with sulfadiazine. The highest risk of such reactions occurs during the first weeks of treatment. Treatment should be discontinued at the first signs of hypersensitivity (progressive skin rashes, often with blisters and mucosal involvement, hematological reactions). Dermazine cream must not be re-administered to such patients. Transient leukopenia may exceptionally occur on days 2–3 after initiation of silver sulfadiazine treatment for burns; this usually resolves within a few days without discontinuation of therapy. Blood parameter monitoring is recommended.

Dermazine cream may be used independently only for minor superficial burns. Patients with deeper burns should always consult a physician before initiating treatment. Burns affecting 2% or more of the body surface area (approximately one patient's palm corresponds to 1% of their body surface area), as well as burns involving the eyes, ears, face, hands, feet, and/or genital area, require medical evaluation.

Medical consultation is required for skin wounds containing foreign materials that cannot be removed, deep puncture wounds, animal bites, wounds with significant redness, sudden onset of swelling, or wounds accompanied by fever.

If prolonged treatment with Dermazine cream over large skin areas is anticipated, blood parameter monitoring is necessary due to the possible development of leukopenia, thrombocytopenia, and eosinophilia. When treating extensive wounds, plasma concentrations of sulfadiazine may reach therapeutic levels, potentially leading to systemic adverse effects of sulfonamides. Therefore, monitoring of sulfadiazine concentration in serum, renal function, and urine for possible crystalluria is recommended.

As with other topical antimicrobial agents, secondary infection may develop during treatment.

Very rarely, an increase in body temperature may occur, related to undesirable side effects.

The excipients methylparahydroxybenzoate and propylparahydroxybenzoate may cause allergic reactions, including delayed-type reactions, and in some cases bronchospasm.

Dermazine contains peanut oil. Patients with hypersensitivity to peanuts or soy should not use this product.

Propylene glycol contained in the formulation may cause skin irritation. Cetyl alcohol may also cause local skin reactions (e.g., contact dermatitis).

The presence of silver ions may cause argyria. Argyria may manifest upon exposure to sunlight (its ultraviolet spectrum) on skin areas where the product has been applied for prolonged periods. To prevent argyria, these skin areas should be protected from direct sunlight (see section "Adverse reactions").

Due to the risk of contamination, the product should preferably be used individually. The cream does not stain clothing or linen and is easily removed during daily wound hygiene procedures.

Use during pregnancy or breastfeeding

Due to limited experience and potential risks (systemically administered sulfonamides displace bilirubin from binding sites on albumin in blood plasma, which may lead to hyperbilirubinemia and kernicterus in newborns), the product should not be used during pregnancy. Silver sulfadiazine should be prescribed with caution to women planning pregnancy.

Sulfonamides are known to increase the risk of bilirubin encephalopathy in infants; therefore, use of the cream is contraindicated during breastfeeding.

Ability to influence reaction rate while driving or operating machinery

No data on adverse effects are available.

Method of Administration and Dosage

The medication is intended for topical external use.

The appropriate treatment regimen should be selected based on an assessment of the size and depth of the wound surface.

After cleaning the burn or other wound surface, apply the cream as a thin layer (2–4 mm) directly onto the affected area (or onto a sterile gauze dressing, which is then applied to the wound surface). The cream should be applied using a sterile spatula or hand wearing a sterile glove, usually once daily; in severe cases, twice daily.

Before each subsequent application, the burn surface should be rinsed with 0.9% sodium chloride solution or an antiseptic solution to remove residual cream and wound exudate. A dressing may be applied.

The method of administration and dosage of the medication does not depend on the patient's age. The medication should be used until complete wound healing or until the wound surface is prepared for appropriate surgical intervention. If the medication is used without medical prescription, consult a physician if the patient's condition does not improve or worsens after 7 days of treatment.

The cream does not stain clothing or bed linen.

Renal/Hepatic Impairment

When applying the cream over large body surface areas, monitor renal and hepatic function and blood parameters (including blood cell counts). The patient should be given abundant alkaline fluids.

Children

Due to the risk of developing kernicterus, silver sulfadiazine must not be used in premature infants, newborns, or children under 3 months of age.

Since the efficacy and safety of the medication in children aged 3 months and older have not been established, its use in this age group is recommended only after consultation with a physician.

Overdose

Signs of intoxication

Overdose with the cream may lead to adverse effects associated with systemic use of all sulfonamides (such as argyria, see section "Adverse Reactions"). Prolonged use of large doses of silver sulfadiazine may increase serum silver levels. However, these levels return to normal after discontinuation of treatment. Overdose may be accompanied by neurological, renal, hepatic, respiratory, and hematological manifestations.

In patients with severe burns undergoing prolonged treatment and receiving more than 10 kg of silver sulfadiazine per day, a significant increase in serum osmolality has been observed. This may be due to propylene glycol (a component of the cream base), which, as a result, enhances drug reabsorption in extensive burns, affecting the skin overall.

Treatment of intoxication

In case of overdose, discontinue the medication immediately. Treat symptomatically. Renal function and blood parameters should be monitored as needed. Absorbed sulfadiazine is readily removed by hemodialysis and peritoneal dialysis.

Side effects

Side effects are listed by frequency: 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 the available data).

Blood system disorders:
Common – leukopenia, methemoglobinemia (especially in patients with hemoglobin abnormalities), increased serum osmolarity.

Transient leukopenia usually does not require discontinuation of therapy or any other special measures. Monitoring of blood parameters in patients is recommended.

Skin and subcutaneous tissue disorders:
Common – hypersensitivity reactions, skin irritation and redness, pruritus, burning sensation, pain upon application, rash, contact dermatitis, skin discoloration to gray under sunlight exposure (argyria – pigmentation caused by silver deposition), photosensitization, skin necrosis;
Very rare – Stevens-Johnson syndrome, toxic epidermal necrolysis;
Frequency not known (cannot be estimated from the available data) – hyperpigmentation, allergic rhinitis and asthma, skin depigmentation, erythema multiforme.

Adverse reactions characteristic of oral sulfadiazine use have been reported during prolonged treatment of large burn surfaces, especially following severe burns, such as nausea, vomiting, diarrhea, glossitis, joint pain, headache, confusion, seizures, anemia, leukopenia, thrombocytopenia, eosinophilia, drug fever, hepatic and/or renal dysfunction, liver necrosis, interstitial nephritis, crystalluria, allergic reactions, skin reactions (purpura, photoallergic dermatoses), nodular erythema, Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, cholestatic hepatosis, folic acid deficiency, agranulocytosis, hepatitis, hypoglycemia, toxic nephrosis. With prolonged use, accumulation of silver in the liver, kidneys, and ocular retina may occur.

Systemic absorption of silver sulfadiazine is very rarely associated with adverse effects related to systemic use of sulfonamides.

Shelf life. 3 years.

Storage conditions.

Store at temperatures not exceeding 25 °C.

Keep out of reach of children.

Packaging.

50 g of cream in a tube; 1 tube per cardboard box.

Prescription status.

Over-the-counter (without prescription).

Manufacturer.

Salutas Pharma GmbH.

Manufacturer's address and location of operations.

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