Argosulfan cream 20 mg/g tube 40 g

Pharmacodynamics. The mechanism of antimicrobial action of sulfathiazole includes inhibition of growth and reproduction of microorganisms, associated with competitive antagonism with para-aminobenzoic acid and inhibition of dihydropteroate synthetase, which leads to disruption of the synthesis of dihydrofolic acid, and, ultimately, its active metabolite – tetrahydrofolic acid, necessary for the synthesis of purines and pyrimidines in the microbial cell.

Silver sulfathiazole has a broad spectrum of antibacterial activity against mixed flora (gram-positive and gram-negative microorganisms), including Pseudomonas aeruginosa.

Inactivates and significantly reduces the infectious ability of herpes and herpes zoster viruses outside the cell.

The drug effectively protects the wound from infection, forms a protective layer on the wound surface, maintains adequate moisture and promotes wound healing.

Pharmacokinetics. Silver sulfathiazole has the lowest solubility among other silver salts of the sulfonamide group, as well as high stability. The low solubility and high stability of silver sulfathiazole allows it to remain on the surface of the affected skin and reduce absorption into the blood. Absorbed sulfathiazole is acetylated in the liver, after which it is excreted in the urine as inactive metabolites and partially unchanged. Absorption of sulfathiazole increases after application of the drug to large areas of affected skin.

Burns of all degrees of severity of various origins (including thermal, solar, chemical, electric shock, radiation), as well as frostbite.

Pressure sores, trophic ulcers of the lower legs of various genesis (including chronic venous insufficiency, obliterating endarteritis, blood supply disorders in diabetes mellitus, pica).

Purulent wounds, household injuries (cuts, abrasions).

Infected dermatitis, contact dermatitis, complicated impetigo, microbial eczema, strepto- and staphyloderma.

Use in burns. The drug is intended for topical use both in an open way and with the use of occlusive dressings. Argosulfan does not cause darkening of the skin and whiteness.

After cleaning and surgical treatment of the wound, the cream is applied in a 2-3 mm layer, observing sterile conditions. All affected skin areas should be covered with the cream throughout the treatment period. If for some reason part of the wound is not covered with the cream, a thin layer of the drug should always be applied additionally. There is no need to apply an occlusive dressing to the wound, except in cases where there are indications for its use. The cream should be applied until the wound is completely healed or until the wound surface is prepared for skin grafting (surgical interventions).

Treatment of bedsores and trophic ulcers of the lower leg. The drug is applied in a thin layer to the affected areas of the skin 2-3 times a day.

If the drug is applied to infected wounds, exudate may appear. In such cases, before applying the cream, the wound should be washed with a 0.1% aqueous solution of chlorhexidine, a 3% aqueous solution of boric acid or another antiseptic. For adults, dosage control is not required.

Hypersensitivity to sulfathiazole, other sulfonamides or excipients, as well as porphyria. Congenital deficiency of glucose-6-phosphate dehydrogenase.

The drug is usually well tolerated.

Skin irritation is noted, which is manifested by a burning sensation at the site of application of the cream. In case of prolonged use of the drug Argosulfan, kidney dysfunction may develop, including interstitial nephritis, dysfunction of the hematopoietic system, including agranulocytosis, hemorrhagic diathesis, thrombocytopenia, aplastic and hemolytic anemia, leukopenia. Irritation and hypersensitivity reactions are possible at the site of application of the cream, including burning, itching, redness. The drug contains cetostearyl alcohol, which can cause the development of local skin reactions, including contact dermatitis. The drug contains propyl parahydroxybenzoate, methyl parahydroxybenzoate, which can lead to the development of allergic reactions.

When using drugs containing silver sulfathiazole, one should be aware of the possibility of hypersensitivity reactions, including Stevens-Johnson syndrome, or other systemic adverse reactions characteristic of sulfonamides, including adverse reactions from the liver.

Cross-hypersensitivity to sulfonylurea derivatives, benzothiazine and p-aminosalicylic acid is possible. In each case, a careful allergic history should be taken, especially to sulfonamides. Avoid contact of the drug with eyes and mucous membranes. In case of accidental contact, rinse with plenty of water. It is also possible to develop undesirable and systemic side effects characteristic of sulfonamides.

The drug should be used with caution in patients in shock after extensive burns or patients after burns who are difficult to contact. Cumulation of the drug and the occurrence of adverse reactions are possible in patients with impaired liver and kidney function.

During prolonged use on large areas of skin, the level of sulfathiazole in the blood plasma should be monitored, especially in cases of kidney and liver diseases, as well as the level of leukocytes, since the development of agranulocytosis or anemia is possible.

Use during pregnancy and breastfeeding. The safety of Argosulfan during pregnancy has not been studied. Animal studies of the effects of silver sulfathiazole on fetal development have not been conducted. Controlled studies of the effects of topical application of the drug on fetal development have not been conducted. It is not recommended to use the drug during pregnancy, except in cases where the expected benefit to the mother outweighs the potential risk to the fetus.

It is not known whether silver sulfathiazole or its metabolites are excreted in human milk. Oral sulfonamides are known to be excreted in human milk and may cause jaundice in infants.

It is not recommended to use the drug during breastfeeding.

Children. The drug can be used in children from 3 months of age.

Ability to influence the reaction rate when driving vehicles or working with other mechanisms. Argosulfan does not affect the ability to drive vehicles or use mechanisms.

The drug is not recommended for use simultaneously with other topical medications to prevent the possibility of their interaction.

When used systemically, folic acid or p-aminosalicylic acid derivatives (e.g. procaine) may weaken the antibacterial effect of silver sulfathiazole.

The frequency of the above interactions is possible, but unlikely, since silver salts of sulfonamides act mainly on the cell membrane, and not on metabolic processes (but such an effect cannot be excluded).

Leukopenia may develop during concomitant treatment with cimetidine (leukopenia is noted 20 times more often in the case of combination with sulfadiazine).

No cases of overdose have been reported. Absorption through damaged skin or increased severity of adverse reactions characteristic of sulfadiazine is possible.

At a temperature not exceeding 25 °C. Do not freeze.

Today, long-term non-healing wounds of various origins are an important problem in medicine. Pressure ulcers and trophic ulcers significantly worsen the patient’s quality of life. In addition to pain and aesthetic discomfort, the wound surface that has existed for a long time becomes a constant source of chronic inflammatory reactions, which, in turn, can lead to exacerbation of concomitant diseases. In addition, microorganisms in the wound can pose a direct threat to human life and health, as they can cause septic complications.

The problem of long-term non-healing wounds and bedsores is especially relevant for bedridden patients, regardless of whether the patient has reached old age or is young or middle-aged and has been immobilized for a long period of time. Bedsores create discomfort for both the patient himself and those who care for him. That is why a drug is needed that would simplify the process of caring for the wound surface and accelerate its healing. Such a drug can be Argosulfan cream, the effectiveness of which is associated with the active substance included in its composition.

In what cases is Argosulfan used:

• Argosulfan is recommended for the treatment of all types of skin burns – thermal, electrical, radiation, chemical (after eliminating the harmful factor), as well as for the treatment of local frostbite of the skin (for example, after removing superficial neoplasms with liquid nitrogen). The drug can be used until the burn wound is completely healed or until the patient is ready for skin flap transplantation. Moreover, this method has proven itself for a long time – occlusive dressings with sulfathiazole have been used since the first half of the twentieth century (Ackman D., 1944);

• in addition, the astringent properties of silver (Fox CL, 1979) allow the drug to be used to treat superficial skin burns, even if the patient did not seek medical attention immediately and the burn wound is already infected;

• an excellent effect in the healing of trophic ulcers is observed in the study of a laboratory model of diabetic foot – a complex multicomponent pathological process, in which an important role is played by microangiopathy (disorder of capillary blood flow in soft tissues). Silver reduces the amount of wound detritus and accelerates the epithelialization of the wound defect, and sulfathiazole inhibits the growth of opportunistic microflora (Zinov’ev EV, 2014);

• a good therapeutic effect is also observed in trophic ulcers of the lower extremities of non-diabetic genesis (for example, severe complications of post-thrombophlebitic syndrome, chronic venous insufficiency or obliterating endarteritis) (Filipiuk J., 1978);

• Argosulfan is effective for the treatment of bedsores. However, bedsores are a complex pathology, the basis of which is a violation of the protective properties and trophicity of soft tissues due to the fact that the same areas are constantly compressed under the weight of the body of a lying person. Therefore, treatment with a combined antibiotic must necessarily be combined with maximum activation of the patient (or regular change of body position in bed), as well as special devices (pillows, mattresses) for load redistribution;

• silver sulfathiazole can be used for skin lesions caused by herpes viruses type 1 or 2 (Stozkowska W., 1999) – studies have shown that a 30-minute exposure to the drug completely inactivates the virus. At the same time, silver provides a direct antiviral effect, and sulfathiazole prevents suppuration or the accession of a bacterial infection. The literature also describes the activity of sulfathiazole against herpes virus type 8, which causes Kaposi’s sarcoma (Angius F. 2017);

• by analogy with other sulfathiazole-containing drugs (Ackman D., 1942) Argosulfan can be used in gynecological practice. For maximum therapeutic effect, it is necessary to combine local antibacterial therapy (Fogli IC, 1954) with systemic use of drugs taking into account the sensitivity of the pathogen (Borno R., 1958). Information has been published on the possibility of using a similar regimen for the treatment of gonorrheal vulvovaginitis (Greig GH, 1941);

• since sulfathiazole is active against staphylococci and streptococci, the drug can be used as an adjuvant in the fistulous form of osteomyelitis (Basch F., 1949) – it is placed in the fistula cavity. In an experiment on dogs, it was proven (Summers L., 1976) that when in contact with the periosteum and adjacent tissues, sulfathiazole has an irritating and stimulating effect and thus promotes the growth of fibrous tissue;

• Argosulfan can also be used in dermatological practice. The method of treating some dermatoses by local application of sulfathiazole preparations has already become classic (Ingels AE, 1943);

• the drug can be used in surgical ENT practice. It can be instilled into the accessory sinuses (Berdal P., 1945) in the surgical treatment of purulent sinusitis, as well as for wound sanitation in mastoiditis (Berdal P., 1945);

• Argosulfan can also be used to treat minor skin injuries (abrasions, scratches), including in children. The latter is especially convenient because the application of the drug is not accompanied by burning (like other antiseptics) and does not stain the skin or clothing.

Method of application of Argosulfan

The drug is applied directly to the wound surface 2 or 3 times a day so that the entire wound is covered with a thin layer of cream. If the wound is infected, then at the initial stage of treatment a large amount of exudate may appear. When dressing, it is necessary to first remove the exudate and residues of Argosulfan after previous application. The optimal solution is a 3% hydrogen peroxide solution, since it is effective for mechanical wound cleaning and has the property of binding sulfathiazole molecules (Zhu G., 2019). As alternative means for washing the wound before applying the cream, it is recommended to use a 3% aqueous solution of boric acid or a 0.1% aqueous solution of chlorhexidine (instructions of the Ministry of Health of Ukraine).

If it is necessary to wash long-term non-healing wounds with an antiseptic between applications of Argosulfan, then it is contraindicated to use methylene blue for these purposes. This feature is due to the fact that methylene blue is an antagonist of sulfathiazole and when used together, these substances neutralize each other (Gots JS, 1949). For the same reason, local anesthetics such as procaine should not be used in combination with the drug.

When selecting physiotherapeutic procedures for the complex treatment of patients, it is necessary to take into account that the effectiveness of sulfathiazole is sharply reduced under the influence of electric current due to oxidative degradation of the active substance (Baran W., 2018). Therefore, Argosulfan cannot be combined with such procedures as electrophoresis, diadynamic therapy (DDT), etc.

The duration of treatment is determined individually. Usually the cream is applied until the pressure ulcer is completely healed or until the wound surface is prepared for skin flap transplantation. The advantages of Argosulfan also include the fact that it does not stain the skin and other tissues and allows for an adequate visual assessment of their condition.

Pharmacological properties and application features

Argosulfan is characterized by a wide spectrum of antibacterial action due to the active ingredient silver sulfathiazole (instructions of the Ministry of Health of Ukraine), which is active against most gram-negative pathogens. Also sensitive to the drug are such pathogens as Shigella flexneri (Butitta PL, 1952), Streptococcus mitis (Clapper WE, 1954), Streptococcus faecalis (Collier HOJ, 1952), Staphylococcus aureus (Daniel RA, 1943), including hemolytic strains, Proteus vulgaris, Bacillus subtilis (Crandall RE, 1948), Pseudomonas spp. (Al-Izzi SA, 1989).

Studies of the molecular structure have shown that silver sulfathiazole forms a polymer film, which provides its unique properties, which are not characteristic of other sulfonamide salts of metals (Fox CL Jr., 1979). Sulfathiazole, by analogy with other drugs from the sulfonamide group, interferes with the metabolism of the microbial cell by blocking the synthesis of folic acid and its active form – tetrahydrofolate. These substances are necessary for the synthesis of purines and pyrimidines, which are responsible for the growth and reproduction of unicellular microorganisms.

The silver ion has the properties to enhance the action of sulfathiazole and reduce the allergenic properties characteristic of sulfonamides. In addition, silver has an inherent bactericidal effect, which is realized through the inhibition of bacterial DNA replication.

Argosulfan can be used for open wound therapy, there is no need to apply an occlusive dressing to the wound, except in cases where there are indications for its use. Due to the formation of a film, the drug protects the wound from dirt and foreign objects. In addition, the film limits water evaporation – drying of the wound surface is excluded.

Dose adjustment for adults is not required, as studies have shown (Waud RA, 1944) that even when applied to an open wound, sulfathiazole practically does not enter the systemic bloodstream. Its diffusion into the tissue is no more than 2-3 mm deep from the wound surface, which guarantees an exclusively local effect.

Silver sulfathiazole is characterized by a minimum degree of solubility and maximum stability compared to other silver salts. Low solubility ensures local action and insignificant absorption of the drug. That small part of sulfathiazole, which nevertheless enters the blood, is partially metabolized in the liver by acetylation, and the rest is excreted unchanged by the kidneys. In addition, sulfathiazole in low doses is secreted into milk (Dai T. 2017), therefore Argosulfan is contraindicated for women during breastfeeding (instructions of the Ministry of Health of Ukraine).

Argosulfan, like other sulfathiazole ointments, can cause individual intolerance reactions. Most often they manifest as eczematous dermatitis or impetigo (Can. Med. Assoc. J., 1944).

It is important to exercise caution when using the drug in patients with burn shock or encephalopathy, as their inadequate condition may cause accidental ingestion of the drug.

With prolonged use of Argosulfan, various reactions of individual intolerance may develop, which must be remembered.

First of all, the drug is categorically contraindicated in patients with congenital deficiency of glucose-6-dehydrogenase. Although Argosulfan is practically not absorbed into the bloodstream, sulfathiazole can still cause the development of hemolytic anemia. For the same reason, the drug cannot be prescribed for the treatment of premature babies and newborns under the age of 3 months. They have a transient deficiency of the above-mentioned enzyme, associated with the peculiarities of fetal hemoglobin metabolism.

In addition, Argosulfan can cause cross-hypersensitivity reactions with derivatives of p-aminosalicylic acid, benzothiazine and sulfonylurea. This fact is especially important, since for bedridden patients the problem of polypharmacy – the simultaneous appointment of a large number of drugs for the treatment of both the main and concomitant pathology – is very relevant.