Modern pharmacological medicine provides a wide range of antimycotic drugs that are used in the treatment of any form of candidiasis. Main active substance most of these drugs are . The pricing policy for such antifungal agents varies greatly depending on the manufacturer, auxiliary components and release forms.

The most effective and inexpensive drug for - fluconazole. The average price for a domestically produced product is 30 – 40 rubles.

General characteristics of the drug

Belongs to the clinical and pharmacological group of antifungal drugs. The main active ingredient of the drug is fluconazole. Its dosage depends on the release form, method of application and can be 50, 100 or 150 mg.

There are several forms of this drug:

• Solutions for infusions. Used to carry out systemic therapy.
• Capsules. Issued No. 1, No. 5 and No. 7. Characterized by high bioavailability.
• Pills. In most cases, they are used to treat chronic fungal pathologies.
• Suspensions. Widely used in pediatrics and to treat people with impaired swallowing reflexes.
• Suppositories. It is one of the most popular forms for the treatment of vaginal candidiasis in women. It has a powerful fungicidal and symptomatic effect.

Depending on the form of release, fluconazole is used for systemic or local treatment of any etiology. For the treatment of thrush, the main causative agent of which is opportunistic yeast fungi of the genus Candida.

The main pharmacological effect of fluconazole is to block the conversion of tetracyclic triterpenoid cells into ergosterol and increase the permeability of cell membranes, which contributes to disruption of their development, growth and replication.

A characteristic feature of the drug is its gentle effect on the body, which is manifested in minimal inhibition of cytochrome enzymes and the complete absence of antiandrogenic activity.

The pharmacokinetics of the drug is manifested in high bioavailability. The active components of the drug freely penetrate into all biological fluids body. Constant values ​​of the concentration of the product in the vaginal secretion are achieved 6 - 8 hours after its use and are retained in its composition for more than a day. It is excreted from the body mainly due to the functionality of the kidneys.

Large selection various forms and dosage of the drug allows you to select the appropriate remedy individually for each patient.

Fluconazole: instructions for use for thrush

The tablet form of the drug is the most common method of any type. Fluconazole tablets are characterized by the presence of a wide spectrum of action. This is ensured thanks to competently selected medicinal components.

In addition to the active substance, their structure contains the following additional substances:

• Stearic acid.
• Sodium dodecyl sulfate.
• Low molecular weight polyvinylpyrrolidone.
• Lactose monohydrate.

All active ingredients of the tablets quickly penetrate the body and cellular structure of opportunistic fungi, which contributes to their rapid destruction. The regimen for taking fluconazole is prescribed strictly by the doctor, taking into account the degree of development of thrush and age category female patients.

Use of the tablet form of the drug:

• The initial stage of the disease is a single dose of 1 tablet of 150 mg dosage.
• In the presence of severe symptoms and against the background of concomitant pathologies, it is prescribed in two doses of 150 mg, every three days.
• Recurrent form - a therapeutic course of three 150 mg tablets is prescribed on the first, fourth and seventh days.
• Chronic candidiasis - take 1 tablet daily for 3 to 6 months.
• For the treatment of a sexual partner - a single dose of 150 mg tablet.
• In pediatrics, but not earlier than 6 years of age - a single dose of 50 mg tablet.
• Prevention – a single dose of 100 mg tablet per quarter.
• “Shock” therapy consists of taking a safocid tablet, which contains fluconazole, azithromycin and secnidazole.

Incorrect use of tablets fluconazole can provoke the emergence of multi-resistant strains of the fungus, which is resistant to almost all pharmacological groups of drugs. Therefore, before taking fluconazole for thrush, it is recommended be sure to consult a doctor.

Fluconazole suppositories: instructions for use

One of the most popular medications used in the treatment of vaginal candidiasis in women is fluconazole in the form of a suppository. This modernized method of treating thrush helps to quickly and effectively provide therapeutic effect directly, both at the site of infection and at the body as a whole. After its active substances penetrate inside, an active fight against the cells of opportunistic fungi that have infected the body begins.

Fluconazole suppositories belong to the Trizol group of drugs. This is a potent medication that has a wide range of effects in the treatment of thrush. Their main advantage is that they are harmless to human enzymes.

Mono treatment with intravaginal use of suppositories is prescribed for initial stage development of thrush. If the pathology already has pronounced signs, parallel administration of oral antifungal medications can be prescribed.

Application of suppository:

• Enter 1 pc. deep into the vagina twice a day.
• If possible, it is recommended to pre-douche using antiseptic and antimycotic agents.
• On average, the course of treatment is 7–10 days.
• During antifungal therapy for vaginal candidiasis, it is recommended to completely abstain from sexual activity for a month.

When treating thrush, fluconazole suppositories will help to quickly cure this disease and quickly neutralize all sensations of unpleasant symptoms. Install correct scheme Treatment and dosage of fluconazole in the form of a suppository should only be done by a doctor specializing in the treatment of this disease.

Fluconazole: applications of injection solutions

Fluconazole in the form of solutions for infusion is a broad-spectrum antifungal drug. Available in bottles of 50 or 100 ml. The pharmacological composition of the drug per 1 ml of the drug is 0.2 g active substance– fluconazole, as well as water for injection and sodium chloride.

Prescribed for:

• Diagnosing thrush of the mucous membranes of the oral cavity, skin and internal organs.
• Treatment of genital and vaginal candidiasis in women.
• Therapy for the urogenital form of thrush in men.
• Carrying out preventive measures, the main goal of which is to prevent the development of oropharyngeal thrush.

Therapeutic course using fluconazole in the form of a solution for intravenous administration can be long-term and continue until the clinical and laboratory effect is fully achieved. The treatment regimen for thrush and the dosage of the drug are prescribed by the doctor, taking into account the etiology and severity of the fungal infection.

Daily doses for various types of thrush:

• Oral and internal organs: 200 – 400 ml. Course 2-3 weeks.
• Vaginal and urogenital: 100 – 150 ml. Duration of treatment is 10 – 20 days.
• Chronic: daily use of 50 – 100 ml for 4 weeks.
• In pediatrics for newborns, no more than 12 mg per 1 kg is calculated. Over 3 years of age, the daily intake should not exceed 200 mg.

Despite the gentle effect on the body of fluconazole in the form of a solution for infusion, it should be used with extreme caution for the treatment of thrush during pregnancy. In this case, self-medication is strictly prohibited. This can provoke not only the development of more complex forms of the disease, but also infection of the fetus.

To enhance the effectiveness of the drug, it is recommended to use it in combination with antimycotics local action , if there is evidence for this. Also speed up the healing process and make it easier negative impact will help fungal infection on the body parallel use of antiseptic, anti-inflammatory and immunomodulatory drugs.

When treating thrush, the prescription of fluconazole in any form can only be recommended by a doctor. Despite the high effectiveness of the drug, its improper use can provoke complications of any form of candidiasis and cause relapse of the disease. According to the clinical picture, fluconazole can be taken for thrush at any time of the day, regardless of meals. The high medicinal properties of the drug do not lose their effectiveness due to this.

There are choices when treating thrush suitable drug- “Clotrimazole” or “Fluconazole”. To answer the question, you need to familiarize yourself with each drug separately and make a comparison in terms of composition, price and, most importantly, side effects. These drugs are aimed at one thing - fighting the fungus. But like any pharmaceutical product, they have advantages and disadvantages.

Comparison

To choose the right drug for thrush, you need to familiarize yourself with their characteristics, evaluate the degree of action and side effects. Each medicine has individual properties, and if it suits one patient and copes with the problem, for another it can cause allergies or worsen the course of the disease. The packaging of each medicine contains instructions that detail the necessary information. By familiarizing yourself with the information on the medicine, you can avoid the consequences and do right choice.

Composition of drugs

Topical preparations cause minimal harm to the body.

The active ingredients in the drugs are clotrimazole and fluconazole, according to the name of the drugs. The excipients are lactose monohydrate, sodium lauryl sulfate, magnesium stearate, potato starch. The drugs are produced in the form of tablets for internal use, vaginal and ointments. The set of excipients depends on the form. The choice of drug form depends on the location and type of disease.

Indications

Before using any medicine, you should consult your doctor to determine correct diagnosis and the choice of active substance for the treatment of fungus.

The main task of these drugs is to fight fungus. "Clotrimazole" is also used to treat birth canal before the birth of a child for the purpose of prevention. Accordingly, fungal diseases are treated with the help of the substances clotrimazole and fluconazole various kinds both skin and mucous membranes, namely:

• fungal skin diseases;
• candidiasis of the mucous membranes of the oral cavity and pharynx;
• vaginal thrush;
• pityriasis rosea;
• stomatitis;
• mycoses, etc.

How to use?

The release of the drug in the form of an ointment makes it convenient to use for the treatment of thrush in men.

Fluconazole and Clotrimazole suppositories are administered vaginally at night. If treatment is started at early stage, then just one candle is enough and the thrush goes away in a couple of days. If the disease is progressive, complex treatment may be required. The use of suppositories for thrush during menstruation is prohibited. Often used with suppositories based on clotrimazole and an ointment with the same components, which is applied to the external genitalia and used to treat thrush in men.

An effective remedy is Fluconazole tablets for internal use. One tablet is enough to overcome the disease at the initial stage. The tablet is quickly absorbed into the body tissues and remains in the blood for a long time. If the disease is chronic, it will take more time, so the course of taking the drug will be longer. It is necessary to repeat taking the tablet after 3 days. The course of treatment is prescribed only by a doctor.

Contraindications

Both drugs - Clotrimazole and Fluconazole - have the same contraindications:

• sensitivity to the active ingredient;
• first 3 months of pregnancy;
• breastfeeding period;
• use in children under 5 years of age.

Side effects

Patients prone to allergies should use the medicine under the supervision of a doctor.

Side effects that may occur when using Fluconazole are dizziness, headache, nausea, vomiting, possible abdominal pain, tachycardia, and skin rashes. With prolonged and improper use, health problems may appear in the form of liver failure, hepatitis, jaundice, and hypertension. Deterioration appears taste sensations.

Side effects from Clotrimazole are an allergic reaction caused by the components of the drug, urticaria. When applied topically, swelling, redness, dryness and flaking of the skin are possible. Women may experience vaginal discharge, inflammation bladder. When treating fungal diseases of the oral cavity, redness, swelling and burning of the oral mucosa are possible.

The present invention relates to medicine, namely to pharmaceutical compositions for local application containing fluconazole and/or ketoconazole and/or terbinafine and liposomes.

Recently, liposomes are most often used as carriers for various biologically active substances, such as vitamins, antibiotics, fruit acids and others, in medicine. The range of liposomal medicines There are ointments, creams and gels for the treatment of various diseases.

Fluconazole (2-(2,4-difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)-2-propanol is an antifungal drug of the chemical group - triazole derivatives. Active against a number of yeasts fungi, dermatophytes and pathogens of opportunistic and endemic mycoses. Used for various fungal infections: for cryptococcosis, including cryptococcal meningitis; for systemic candidiasis, candidiasis of the mucous membranes, vaginal candidiasis; malignant neoplasms when treating them with cytostatics or conducting radiation therapy, in patients with AIDS, during organ transplantation and in other cases when the immune system is suppressed and there is a danger of developing a fungal infection. Prescribed orally and intravenously. Medicines containing fluconazole for topical use are not described.

Ketoconazole (1-cis-1-acetyl-4-para- - methoxyphenyl-piperazine - an antifungal drug of the chemical group - imidazole derivatives. Active against dermatophytes, yeast-like and mold fungi, causative agents of systemic mycoses, as well as leishmania. Prescribed for superficial and systemic mycoses: dermatomycosis and onychomycosis caused by blastomycetes; mycosis of the scalp, vaginal mycosis; blastomycosis of the oral cavity and gastrointestinal tract, genitourinary organs, histoplasmosis and other mycoses of internal organs, as well as for purulent leishmaniasis. Used internally and topically. % shampoo in bottles of 25 and 60 ml; 2% cream in tubes of 15 g; 2% ointment in tubes of 20, 30, 40 and 50 g; vaginal suppositories of 0.4 g.

Terbinafine (E) - N-(6,6-dimethyl-2-hepten-4-inyl)-N-methyl-1-naphthylmethylamine - an antifungal drug of the chemical group - N-methylnaphthalene derivatives. When applied topically (in the form of a cream or solution), it is poorly absorbed and has little systemic effect; quickly diffuses through the skin and accumulates in sebaceous glands; excreted with sebum, while creating relatively high concentrations in hair follicles and hair.

within a few weeks after the start of treatment, it also penetrates into the nail plates. Prescribed for onychomycosis, dermatomycosis, mycosis of the scalp, candidiasis of the skin and mucous membranes. Use internally and externally. Described for external use: 1% solution and spray in bottles of 15 and 30 ml; 1% cream in tubes of 10, 15 and 30 g.

The disadvantage of the above products is that they do not penetrate the skin well and, therefore, when applied topically, are effective only in its superficial layers.

Essaven gel is known, which includes: escin, “essential” phospholipids and heparin sodium salt and used for phlebitis, thrombophlebitis and hemorrhoids (Mashkovsky M.D. Medicines. - 15th ed., revised, revised and supplemented. - M.: Novaya Volna, 2006. - p. 461-462).

Pharmaceutical compositions containing fluconazole and/or ketoconazole and/or terbinafine and liposomes are not described for topical use.

Thus, the object of the present invention is to provide a pharmaceutical composition for topical use containing fluconazole and/or ketoconazole and/or terbinafine and liposomes, having rapid penetration through the skin.

According to the present invention, a pharmaceutical composition for topical use is provided, containing fluconazole and/or ketoconazole and/or terbinafine and pharmaceutically acceptable carriers or excipients, characterized in that it additionally includes liposomes.

As a preferred embodiment of the claimed invention, a pharmaceutical composition is proposed that has next lineup, wt.%:

As another preferred embodiment of the claimed invention, a pharmaceutical composition is proposed, which has the following composition, wt.%:

The technical result of the present invention is the production of a pharmaceutical composition based on fluconazole and/or ketoconazole and/or terbinafine and liposomes, which has the ability to quickly penetrate the skin and, accordingly, rapid absorption. Additional advantages are also ease of use and ease of dosing.

The pharmaceutical composition of the present invention is generally prepared by conventional methods using solid or liquid pharmaceutically acceptable carriers or excipients selected from emulsifiers, dispersing agents, preservatives, flavorings, pH adjusters, polymeric carriers and other excipients that are useful for the preparation of compositions for topical use. The pharmaceutical composition of the present invention can be prepared in the form of a gel, cream, ointment and the like.

Rapid penetration through the skin is due to the binding of fluconazole and/or ketoconazole and/or terbinafine to liposomes containing hydrogenated lecithins in combination with cholesterol.

In preferred embodiments, the compositions are oriented: in the first case - for the treatment of candidiasis, in the second - for the treatment of dermatomycosis and onychomycosis, in the third - dermatomycosis, the binding of active substances to liposomes ensures their stability and duration of action, as well as penetration into the deep layers of tissues affected by fungal flora .

The present invention is illustrated by the following examples.

The pharmaceutical composition in the form of a cream based on fluconazole and liposomes has the following composition:

The specified composition is prepared according to the following procedure. In demineralized water when heated to 80°C, the following are mixed: fluconazole, carbomer, emulsifier, then cooled to 30°C and liposomes and a preservative are added. The resulting cream is homogenized and vacuumized.

The pharmaceutical composition in the form of a cream based on ketoconazole and liposomes has the following composition:

The specified composition is prepared as in EXAMPLE 1, it differs in that ketoconazole is used instead of fluconazole.

The pharmaceutical composition in the form of a cream based on terbinafine and liposomes has the following composition:

The specified composition is prepared as in EXAMPLE 1, it differs in that terbinafine is used instead of fluconazole.

Study of a pharmaceutical composition with fluconazole and liposomes for the ability to quickly penetrate the skin.

To this end, the rapid skin penetration ability of the fluconazole-based composition of the present invention was compared with a control composition containing fluconazole without liposomes. Tests were carried out on rabbits. These compositions were applied to inner surface rabbit ear. Absorption was determined by the amount of fluconazole remaining on the rabbit's skin 10 minutes after application of the compositions, and was expressed as a percentage of the initial amount of fluconazole in the composition.

Study results: control composition - 50% of the remaining fluconazole; the composition of the present invention is 10% of the remaining fluconazole. Similar results were obtained when studying compositions from examples 2 and 3.

Thus, the pharmaceutical composition of this invention has the ability to quickly penetrate the skin, providing faster manifestation therapeutic effect provided by the active substances of the composition.

1. Pharmaceutical composition for topical use, characterized in that it contains fluconazole, liposomes, emulsifier, preservative, demineralized water in the following ratio, wt.%:

2. Pharmaceutical composition for topical use, characterized in that it contains ketoconazole, liposomes, emulsifier, preservative, demineralized water in the following ratio, wt.%:

3. Pharmaceutical composition for topical use, characterized in that it contains terbinafine, liposomes, emulsifier, preservative, demineralized water in the following ratio, wt.%:

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Classification of antifungal drugs

Antifungal drugs classified by chemical structure, characteristics of the spectrum of activity, pharmacokinetics and clinical application for various mycoses.

I. Polyenes:

- nystatin

— levorin

- natamycin

— amphotericin B

— amphotericin B liposomal.

For systemic use

- ketoconazole

- fluconazole

— itraconazole

For topical use

- clotrimazole

- miconazole

- bifonazole

- econazole

- isoconazole

- oxiconazole.

III. Allylamines:

For systemic use

- terbinafine

For topical use

- Naftifine.

IV. Drugs of different groups:

For systemic use

- griseofulvin

- potassium iodide

For topical use

- fmorolfine

- ciclopirox.

Polyenes

Polyenes that are natural antimycotics include nystatin, levorin and natamycin, used topically and orally, as well as amphotericin B, used primarily for the treatment of severe systemic mycoses. Liposomal amphotericin B is one of the modern dosage forms of this polyene with improved tolerability. It is obtained by encapsulating amphotericin B in liposomes (fat bubbles formed when phospholipids are dispersed in water), which ensures the release of the active substance only upon contact with fungal cells and its inactivity in relation to normal tissues.

Mechanism of action.

Polyenes, depending on the concentration, can have both fungistatic and fungicidal effects due to the binding of the drug to the ergosterol of the fungal membrane, which leads to a violation of its integrity, loss of cytoplasmic contents and cell death.

Adverse reactions.

Nystatin, levorin, natamycin

- for systemic use:

Gastrointestinal tract: abdominal pain, nausea, vomiting, diarrhea.

Allergic reactions: rash, itching, Stevens-Jones syndrome (rare).

- for local use:

irritation of the skin and mucous membranes, accompanied by a burning sensation.

Amphotericin B.

Reactions to intravenous infusion: fever, chills, nausea, vomiting, headache, hypotension. Preventive measures: premedication with non-steroidal anti-inflammatory drugs (paracetamol, ibuprofen) and antihistamines (diphenhydramine).

Local reactions: pain at the infusion site, phlebitis, thrombophlebitis. Preventive measures: administration of heparin.

Kidneys: dysfunction - decreased diuresis or polyuria. Control measures: monitoring clinical analysis urine.

Gastrointestinal tract: abdominal pain, anorexia, nausea, vomiting, diarrhea.

Nervous system: headache, dizziness, paresis, sensory disturbances, tremor, convulsions.

Allergic reactions: rash, itching, bronchospasm.

Amphotericin B liposomal.

Compared to the standard drug, it is less likely to cause anemia, fever, chills, hypotension, and is less nephrotoxic.

Indications.

Nystatin, levorin.

Vulvovaginal candidiasis.

Prophylactic use is ineffective!

Natamycin.

Candidiasis of the skin, mouth and pharynx, intestines.

Vulvovaginal candidiasis.

Candidiasis balanoposthitis.

Trichomonas vulvovaginitis.

Amphotericin B.

Severe forms of systemic mycoses:

- invasive candidiasis;

— aspergillosis;

- cryptococcosis;

- sporotrichosis;

- mucormycosis;

- trichosporosis;

— fusarium;

- phaeohyphomycosis;

- endemic mycoses (blastomycosis, coccidiosis, paracoccidioidosis, histoplasmosis, penicillium).

Candidiasis of the skin and mucous membranes (local.

Leishmaniasis.

Primary amebic meninoencephalitis caused by N. fowleri.

Amphotericin B liposomal.

Severe forms of systemic mycoses (see amphotericin B) in patients with kidney failure, with the ineffectiveness of the standard drug, with its nephrotoxicity or severe reactions to intravenous infusion that cannot be controlled by premedication.

Contraindications.

For all polyenes:

- allergic reactions to drugs of the polyene group.

Additionally for amphotericin B:

- liver dysfunction;

- renal dysfunction;

— diabetes mellitus.

All contraindications are relative, since amphotericin B is almost always used for health reasons.

Azoles

Azoles are the most representative group of synthetic antimycotics, including drugs for systemic ( ketoconazole, fulconazole, itraconazole) and local ( bifonazole, isoconazole, clotrimazole, miconazole, oxyconazole, econazole) applications. It should be noted that the first of the proposed “systemic” azoles, ketoconazole, after administration into clinical practice itraconazole has practically lost its importance due to high toxicity and has recently been more often used topically.

Mechanism of action.

Azoles have a predominantly fungistatic effect, which is associated with inhibition of cytochrome P-450-dependent 14-demethylase, which catalyzes the conversion of lanosterol to ergosterol, the main structural component of the fungal membrane. Local preparations when creating high local concentrations, they can act fungicidal against a number of fungi.

Adverse reactions.

Common to all systemic azoles:

Gastrointestinal tract: abdominal pain, loss of appetite, nausea, vomiting, diarrhea, constipation.

CNS: headache, dizziness, drowsiness, visual disturbances, paresthesia, tremor, convulsions.

Allergic reactions: rash, itching, exfoliative dermatitis, Stevens-Johnson syndrome (more often when using fluconazole).

Hematological reactions: thrombocytopenia, agranulocytosis.

Liver: increased transaminase activity, cholestatic jaundice.

Common for topical azoles:

For intravaginal use: itching, burning, hyperemia and swelling of the mucous membrane, vaginal discharge, increased urination, pain during sexual intercourse, a burning sensation in the penis of the sexual partner.

Indications.

Intraconazole.

Dermatomycoses:

- epidermophytosis;

- trichovitia;

- mycosporia.

Pityriasis versicolor.

Candidiasis of the esophagus, skin and mucous membranes, nails, candidal paronychia, vulvovaginitis.

Cryptococcosis.

Aspergillosis (with resistance or poor tolerance to amphotericin B).

Pseudoallescheriosis.

Pheohyphomycosis.

Chromomycosis.

Sporotrichosis.

Endemic mycoses.

Prevention of mycoses in AIDS.

Invasive candidiasis.

Candidiasis of the skin, mucous membranes, esophagus, candidal paronychia, onychomycosis, vulvovaginitis).

Cryptococcosis.

Dermatomycoses:

- epidermophytosis;

- trichovitia;

- mycosporia.

Pityriasis versicolor.

Sporotrichosis.

Pseudoallescheriosis.

Trichosporosis.

Some endemic mycoses.

Candidiasis of the skin, esophagus, candidal paronychia, vulvovaginitis.

Pityriasis versicolor (systemic and local).

Dermatomycosis (locally).

Seborrheic eczema (topically).

Paracoccidiosis.

Azoles for topical use.

Candidiasis of the skin, oral cavity and pharynx, vulvovaginal candidiasis.

Dermatomycoses:

- trichophytosis and epidermophytosis of smooth skin;

- hands and feet with limited lesions.

For onisomycosis they are ineffective.

Pityriasis versicolor.

Erythrasma.

Contraindications.

Allergic reaction to drugs of the azole group.

Pregnancy (systemic).

Breastfeeding (systemically).

Severe liver dysfunction (ketoconazole, itraconazole).

Age up to 16 years (itraconazole).

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Antifungal agents of the group - Polyenes:

Among all antifungal drugs, polyenes have the most wide range activity. These include nystatin, natamycin, levorin, amphotericin B. When applied topically, they are active primarily against Candida spp., Natamycin (Pimafucin) is also active against protozoa, for example, Trichomonas. Pseudoallesheria and dermatomycete fungi are resistant to polyenes, that is, the area of ​​application of this group of antimycotic drugs is candidiasis of the mucous membranes, skin, and gastrointestinal tract.

- an antifungal antibiotic from the polyene group, highly active against fungi of the genus Candida. Practically not absorbed into the gastrointestinal tract. Lately it has hardly been used.

• Indications for use: Candidiasis of the skin, intestines, oral cavity and pharynx. Prevention and treatment of gastrointestinal candidiasis arising from long-term treatment antibiotics tetracycline and penicillin series. Prevention of candidiasis in postoperative period in surgery of the gastrointestinal tract.
• Contraindications: Hypersensitivity.
• Side effects: Allergic reactions, nausea, vomiting, abdominal pain, chills, diarrhea.
• Price: 15-50 rub.

Levorin- most active against Candida albicans, protozoa - Trichomonas, amoebas, leishmania. With hypertrophy prostate gland reduces dysuric phenomena, sometimes reduces the size of the adenoma.

• Indications for use: Candidiasis of the skin, intestines, oral cavity and pharynx. Levorin tablets are used for candidiasis, gastrointestinal candidiasis, and prostate hypertrophy as part of complex therapy.
• Contraindications: liver or kidney failure, acute diseases intestines of non-fungal origin, peptic ulcer stomach, pregnancy, pancreatitis. With caution - for children under 2 years of age and during lactation.
• Side effects: Decreased appetite, allergic reactions, nausea, vomiting, headache.

(Natamycin) is an antifungal polyene antibiotic that has a fungicidal effect. Most molds and pathogenic yeasts are sensitive to pimafucin, including the genera Aspergillus, Candida, Fusarium, Cephalosporium, and Penicillium. Pimafucin tablets, coated enteric coated, have an effect only in the intestinal lumen, without exerting systemic action.

• Indications for use: intestinal candidiasis, vaginal candidiasis, acute atrophic candidiasis in patients with immune deficiency, after therapy with corticosteroids, antibiotics, cytostatics. It can be used during pregnancy and breastfeeding.
• Contraindications: increased sensitivity to the components of the drug.
• Side effects: diarrhea, nausea, may occur in the first days of taking the medicine, and go away on their own during treatment.
• Price: average price 400 rub. for 20 tablets

Amphotericin B - analogues of Ambizom, Amphoglucamine, Amfocil, Ampholip, Fungizon are lyophilisates for infusion. Used for life-threatening, progressive fungal infections, disseminated forms of candidiasis, infections abdominal cavity, peritonitis, fungal sepsis.

Antifungal drugs of the Azole group:

Azoles- a group of synthetic antimycotics, including fluconazole, ketoconazole, and itraconazole. After the introduction of itraconazole into practice, ketoconazole lost its importance due to its high toxicity and is currently used mainly only for the local treatment of mycoses. This group of antimycotics is effective in the treatment of certain types of lichen, fungal infections of the skin, nails, scalp, and candidiasis of the mucous membranes.

Analogues Oronazole Mycozoral, Nizoral, Fungavis- a synthetic derivative of imidazoledioxolane, active against yeast-like fungi, dermatophytes, higher fungi and dimorphic fungi.

– analogues Irunin, Itrazol, Kanditral, Orungal, Rumikoz, Orunit. Synthetic antifungal drugs in tablets have a wide spectrum of action against fungi: dermatophytes, yeast fungi Candida spp, mold fungi. The effectiveness of treatment for mycoses should be assessed 2-4 weeks after completion, with treatment with drugs for nail fungus after 6-9 months.

– analogues Vero-fluconazole, Diflucan, Medoflucon, Diflazon, Mikomax, Mikosist, Mikoflucan, Flucostat. Antifungal drugs in tablets with a highly specific effect suppress the activity of fungal enzymes, disrupt their growth and replication.

• Indications for use: Generalized candidiasis with damage to the respiratory organs, abdominal organs, eyes and genitourinary organs. Systemic lesions by Cryptococcus fungi - sepsis, meningitis, lung and skin infections, in patients with various disorders immunity and with a normal immune response. Candidiasis of the mucous membranes of the oral cavity, esophagus, pharynx, non-invasive bronchopulmonary candidiasis. Genital candidiasis, prevention of fungal infections in patients with malignant tumors. Foot fungus, mycoses of the skin: body, nails (onychomycosis), with pityriasis versicolor. Deep endemic mycoses sporotrichosis, coccidioidosis, and histoplasmosis in patients with normal immunity.
• Contraindications: Hypersensitivity, simultaneous use of terfenadine and astemizole, lactation period. Use with caution in patients with liver failure, during pregnancy, people with organic diseases hearts.

• Side effects: Digestive system: nausea, diarrhea, flatulence, abdominal pain, change in taste, impaired liver function. Nervous system: headache, dizziness, convulsions. Hematopoietic organs: neutropenia, leukopenia, thrombocytopenia. Allergic reactions: skin rash, exudative erythema, facial swelling, angioedema, urticaria, skin itching. Cardiovascular system: ventricular fibrillation/flutter, increased duration of the Q-T interval.
• Price: -150 mg. 1 piece - 15 rubles, 50 mg. 7pcs.-32 rub., Diflucan— 150 mg.-720 rub. 50mg 7pcs -850 rub. Mikosist 150 mg. 1 pc. - 270 rub., 50 mg. 7 pcs. — 550 rub. Flucostat-150 mg. 1 pc. - 150 rub., 50 mg. 7 pcs. — 250 rub.

Azole antifungal tablets should be taken with plenty of water and with meals. If the patient has low stomach acidity, these medications must be taken with acidic liquids. When taking systemic azoles, do not take astemizole, terfenadine, pimozide, cisapride, quinidine, lovastatin and simvastatin. Pregnant and lactating women should not use azoles in tablets.

See suppositories for thrush

Antifungal tablets of the group - Allylamines:

Allylamines are synthetic antimycotics, the main indications for use of which are dermatomycosis - fungal diseases of the nails, skin, hair, and lichen.

- analogues Terbinox, Terbizil, Exitern, Bramisil, Lamisil. It is an allylamine with a broad spectrum of action against fungi, causing diseases nails, skin, hair, including dermatophytes. In low concentrations it has an effect on molds and dimorphic fungi.

• Indications for use: mycoses of the scalp, nails (onychomycosis), treatment of dermatomycosis of the legs, torso, feet, in cases where the prevalence of infection is pronounced and oral administration of antifungal agents is indicated. For treatment versicolor Terbinafine is used only as a topical treatment; oral administration is not very effective for this disease.
• Contraindications: Not recommended for patients with active, chronic liver and kidney diseases. Pregnancy and lactation.
• Side effects: Immune system: systemic and cutaneous lupus erythematosus. Nervous system: headache; taste disturbances, dizziness. Digestive system: dyspepsia, feeling of fullness in the stomach, nausea, loss of appetite, abdominal pain, diarrhea. Dermatological reactions: skin reactions, psoriasis-like skin rashes. Musculoskeletal system: arthralgia, myalgia.
• Price: Terbizil 14 pcs 1000 rub., 28 pcs 1800 rub. Lamisil 14 pcs 1800 rub. Terbinox 14 pcs 580 rub. 14 pcs. 480-560 rub.

Terbinafine is taken orally regardless of food intake, it must be taken with a sufficient amount of water. Alcohol consumption is contraindicated during treatment with any oral antifungal drugs.

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Systemic therapy is the most effective and reliable treatment onychomycosis. Systemic therapy is used when treatment local means turns out to be ineffective.

INDICATIONS FOR SYSTEMIC THERAPY

Clinical characteristics of onychomycosis:

clinical form:

distal-lateral (late stages),

proximal,

total;

damage to more than half of the nail;

involvement of the matrix in the process;

pronounced changes in the nail (hyperkeratosis, onycholysis);

damage to more than 2-3 nails

Failure of local therapy

Combination of onychomycosis with widespread skin or hair lesions

Although systemic therapy most often cures onychomycosis, its use is associated with a number of difficulties. When administered systemically, the drug does not enter the nails immediately, but first overcomes numerous obstacles. Its concentration in nails is much less than when applied topically. For this concentration to become effective, i.e. destroyed fungi or suppressed their growth, you can, firstly, increase the concentration as a result of increasing the dose of the drug. However, increasing the dose will increase the risk of side effects and toxic effects. To overcome these difficulties use the latest drugs, accumulating in the nail upon repeated administration. Secondly, you can choose a drug that is effective in low concentrations. Modern drugs with very low MICs for onychomycosis pathogens meet this requirement.

Systemic antifungal drugs

There are only 8 systemic antimycotics. Of these, griseofulvin, terbinafine, ketoconazole and itraconazole are widely used in the treatment of onychomycosis, and fluconazole is currently being introduced into therapy. All these drugs are prescribed orally.

The main criteria that determine the effectiveness of a systemic antifungal drug for onychomycosis:

— antifungal activity and spectrum of action;

- pharmacokinetics (the ability to quickly penetrate the nails, accumulate and linger in them);

- safety.

Not all systemic therapies meet each of these criteria. When prescribing them, one should take into account the characteristics of each case of onychomycosis, the patient’s condition, concomitant diseases and their therapy. Below we present the main characteristics of each drug.

Griseofulvin

The antifungal antibiotic griseofulvin is the first systemic drug for the treatment of dermatophyte infections. Griseofulvin has been used in the treatment of onychomycosis for more than 30 years.

Griseofulvin acts only on dermatophytes; the MIC for them is in the range of 0.1-5 mg/l.

Griseofulvin is not completely absorbed from the gastrointestinal tract; absorption improves when taken with food. In order to improve absorption, micronized (finely divided) and ultramicronized forms have been developed. Taking 500 mg of griseofulvin provides maximum concentrations of 0.5-2.0 mg/l, which does not always exceed the MIC. Treatment of onychomycosis is usually carried out with griseofulvin at a dose of 1000 mg/day.

In the blood, griseofulvin is partially bound to plasma proteins. Metabolism occurs in the liver, more than a third of the drug is excreted in the feces.

Although griseofulvin is a lipophilic substance that can accumulate in tissues, its affinity for keratin is rather low. 48-72 hours after discontinuation of the drug, it is no longer found in the stratum corneum, so treatment of onychomycosis with griseofulvin is carried out continuously, until a healthy nail plate grows. In general, the kinetics of griseofulvin in the nail has been poorly studied.

Griseofulvin for oral administration is available in tablets and in the form of an oral suspension. Tablets contain 125 or 500 mg of griseofulvin, in a package of 25 or 1000 tablets of 125 mg, 25 or 250 tablets of 500 mg. 1 ml of suspension contains 0.1 g of griseofulvin.

Enhanced absorption formulations include micronized griseofulvin (griseofulvin forte), available in 125, 250, or 500 mg tablets, and ultramicronized griseofulvin in 125 mg tablets. In recent decades, micronized forms have been most widely used.

The dose of griseofulvin is determined according to the age and body weight of the patient. The daily dose for adults of the micronized form of griseofulvin for onychomycosis is from 500 to 1000 mg (in 2-4 doses), but not less than 10 mg/kg. The duration of treatment for fingernails is about 4-6 months, for toenails - from 9 to 12, sometimes up to 18 months.

For children weighing less than 25 kg, the daily dose is prescribed at the rate of 10 mg/kg (or in 2 doses of 5 mg/kg), children weighing more than 25 kg are given 250-500 mg/day. In general, it is not recommended to prescribe griseofulvin for the treatment of onychomycosis in children.

When treating with ultramicronized griseofulvin, the dose is reduced by a third or even half.

When prescribing griseofulvin with other drugs, they should be taken into account possible interaction. Barbiturates reduce the absorption of griseofulvin. Griseofulvin weakens the effect indirect anticoagulants, reduces cyclosporine concentrations. It should be remembered that griseofulvin can significantly weaken the effect of hormonal contraceptives.

The most common side effects when taking griseofulvin are nausea, sometimes vomiting, epigastric discomfort, headache and dizziness. In addition, griseofulvin has photosensitizing properties. Toxic effects include effects on the liver, as well as rare cases of agranulocytosis. Griseofulvin is not prescribed to pregnant and nursing mothers.

Terbinafine (Lamisil)

Terbinafine is a synthetic drug from the class of allylamines that has been used in the treatment of onychomycosis since the early 90s.

The average MIC of terbinafine for dermatophytes does not exceed 0.06 mg/l. In addition, terbinafine acts in vitro against many other molds. The effectiveness of terbinafine for non-dermatophyte mold infections is unknown. Many yeasts, in particular Candida albicans, are resistant to terbinafine at MICs up to 128 mg/l.

Terbinafine is well absorbed from the gastrointestinal tract; food intake does not affect absorption. Peak plasma concentrations at doses of 250 and 500 mg are about 0.9 and 1.7-2 mg/l, respectively. This is much higher than the MIC for sensitive fungi. Concentrations are directly dependent on the dose and increase with its increase and with repeated administration of the drug. In the blood, terbinafine binds to proteins of all plasma fractions and to formed elements.

Terbinafine is metabolized in the liver. There are 15 known metabolites, all of them inactive. About 80% of the drug is excreted in the urine. Insufficient liver or kidney function slows elimination.

Terbinafine appears on the distal edges of the nails on average at 8 weeks from the start of treatment. Terbinafine penetrates the nail plate primarily through the matrix, but also through the nail bed. After discontinuation of treatment, terbinafine in effective concentrations remains in the nails for 4-6 weeks.

Terbinafine hydrochloride for oral administration is available in tablets of 125 and 250 mg, in a package of 14 or 28 tablets.

In the treatment of onychomycosis caused by dermatophytes, terbinafine is used at a dose of 250 mg/day. In recent years, terbinafine has been prescribed in short courses: for infections of the fingernails for a period of 6 weeks (1.5 months), for infections of the toenails for a period of 12 weeks (3 months). The effectiveness of terbinafine at a dose of 500 mg per day for 3 months for nail candidiasis was studied. Pulse therapy with terbinafine is possible at a dose of 500 mg/day in one-week courses for 3-4 months.

Doses for children are for body weight up to 20 kg 62.25 mg (half a tablet 125 mg), up to 40 kg - 125 mg, for children weighing more than 40 kg give full dose. Experience in treating children with terbinafine is limited.

When prescribing terbinafine, its possible interaction with drugs metabolized by the liver should be taken into account. Rifampicin reduces, and cimetidine and terfenadine increase, concentrations of terbinafine.

The most common side effects with terbinafine include nausea, a feeling of fullness or abdominal pain, and sometimes decreased appetite. Loss or changes in taste have been reported during treatment. In addition to dyspeptic symptoms, urticaria may develop during treatment with terbinafine. Toxic effects - hepatotoxicity, agranulocytosis, damage to the organ of vision and some others are very rare. Terbinafine should not be prescribed to persons with liver disease. In case of renal failure, the dose of terbinafine should be reduced by half if the creatinine clearance exceeds 50 ml/min. Terbinafine is not prescribed to pregnant and nursing mothers.

Ketoconazole (nizoral, oronazole)

This synthetic drug from the azole class has been used in the treatment of mycoses since the late 70s.

Ketoconazole has a wide spectrum of action. The average MIC for dermatophytes is about 0.1-0.2 mg/l, for Candida albicans - about 0.5 mg/l. Many molds that cause nondermatophytic onychomycosis are resistant to ketoconazole.

Ketoconazole is not completely absorbed from the gastrointestinal tract. Absorption is worse with reduced acidity and improves when taken with food. Taking 200 mg of ketoconazole leads to a peak plasma concentration of about 3 mg/l, taking 400 mg - 5-6 mg/l. These concentrations exceed the MIC for sensitive pathogens.

In the blood, ketoconazole is almost completely bound to plasma proteins and is intensively metabolized in the liver. Metabolites are inactive, most of them are excreted in feces.

Ketoconazole has a high affinity for keratin. The drug enters the nails through the matrix and nail bed; it can be detected on the 11th day from the start of treatment. Although ketoconazole appears to be retained in the nail for some time after treatment is stopped, the kinetics of the drug in the nail have not been well studied.

Ketoconazole for oral administration is available in tablets of 200 mg, in a package of 10, 20 or 30 tablets.

For onychomycosis, ketoconazole is prescribed at a dose of 200 mg/day. It is better to take the drug with food. Treatment takes 4-6 months for onychomycosis of the hands and 8-12 months for onychomycosis of the feet.

For children weighing from 15 to 30 kg, ketoconazole is prescribed 100 mg (half a tablet). Children with greater body weight are given the full dose. In general, ketoconazole should not be used to treat onychomycosis in children.

When prescribing ketoconazole, it is necessary to take into account its possible interaction with many drugs. Antacids and agents that reduce gastric secretion interfere with the absorption of ketoconazole. Ketoconazole increases the half-life of the antihistamines terfenadine, astemizole, and cisapride; sharing These drugs can lead to the development of arrhythmia. Ketoconazole increases the half-life of midazolam, triazolam, cyclosporine and potentiates the effect of indirect anticoagulants. Concentrations of ketoconazole are reduced when administered with rifampicin and isoniazid and change when used with phenytoin.

Common side effects of ketoconazole include nausea, less commonly vomiting, and decreased appetite. By taking the drug with meals or at night, you can avoid these phenomena.

The main toxic effect of ketoconazole is its effect on the liver. An increase in the concentration of liver transaminases during treatment is observed in 5-10% of patients taking ketoconazole. If these phenomena become permanent or intensify, the drug should be discontinued. Severe liver damage is rare, but with long-term treatment of onychomycosis, its likelihood increases. The effect of ketoconazole on steroid metabolism in humans may cause changes in cholesterol levels and steroid hormones in the blood, but these changes do not manifest themselves clinically. Ketoconazole should not be prescribed to pregnant and nursing mothers.

Itraconazole (orungal)

This synthetic drug from the azole class has been used in the treatment of onychomycosis since the early 90s.

The spectrum of action of itraconazole is the widest among all antifungal agents for oral administration. Itraconazole acts on dermatophytes (with an average MIC of about 0.1 mg/l), different types Candida (with MIC in the range of 0.1-1 mg/l) and many molds found in onychomycosis.

Itraconazole is not completely absorbed from the gastrointestinal tract. Absorption of the drug is worse at low acidity, but significantly improves when taken with food. After taking 100 mg of the drug, maximum plasma concentrations are 0.1-0.2 mg/l, increasing to 1 mg/l when taking 200 mg and up to 2 mg/l when taking 400 mg. This exceeds the MIC for most pathogenic fungi.

In the blood, Itraconazole is almost completely bound to plasma proteins and is intensively metabolized in the liver. The main metabolite is hydroxyItraconazole, which is not inferior in activity to itraconazole. Most of the metabolites are excreted in the feces.

The keratophilicity of itraconazole ensures its high concentrations in the skin and nails, 4 times higher than plasma concentrations. At the distal ends of the nail plates, itraconazole can be detected after 1 week of treatment. Itraconazole penetrates into the nail plate both through the matrix and directly through the nail bed. The drug accumulates in the matrix and is excreted only when a new nail plate grows, so the effective concentration of the drug after its discontinuation is maintained in the fingernails for another 3 months, and in the toenails for 6-9 months with a 3-month course of treatment.

Itraconazole for oral administration is available in capsules containing 100 mg of the drug, in a package of 4 or 15 capsules.

It is possible to treat onychomycosis with short courses of 200 mg of itraconazole every day for 3 months. In recent years, the pulse therapy technique has gained greater recognition, when itraconazole is prescribed at a dose of 400 mg/day (in 2 doses) for 1 week. When treating infections on the hands, 2 courses of pulse therapy are prescribed in a one-week course every month. When treating leg infections, 3 or 4 courses are prescribed depending on the shape and severity of the lesion. Itraconazole should be taken with food, no more than 200 mg (2 capsules) per dose. Since experience with itraconazole in pediatrics is limited, recommendations for dosage of the drug in children have not been developed.

When prescribing itraconazole, the risk of interaction with other drugs is taken into account. Antacids and gastric depressants interfere with the absorption of itraconazole. Itraconazole should not be co-administered with astemizole, terfenadine or cisapride due to the potential for arrhythmia. Itraconazole also increases the half-life of midazolam and triazolam, digoxin, cyclosporine, and potentiates the effect of indirect anticoagulants. Rifampicin and phenytoin reduce itraconazole concentrations.

The most common side effects are nausea, epigastric discomfort and abdominal pain, and constipation. A small proportion of patients experience a transient increase in the concentration of liver transaminases. If it does not decrease or symptoms of hepatitis appear, then treatment is stopped. Itraconazole should not be prescribed to patients with liver disease. At the indicated doses, itraconazole has no effect on the metabolism of steroid hormones. Pregnant and nursing mothers are not treated with itraconazole for onychomycosis.

Fluconazole (Diflucan)

Fluconazole is a drug from the azole class, was obtained in 1982. It began to be used for onychomycosis in recent years.

The spectrum of action of fluconazole is wide. The MIC for dermatophytes is up to 1 mg/l, for Candida albicans - 0.25 mg/l. The activity of fluconazole against various molds appears to be less than against yeasts.

Fluconazole is almost completely absorbed from the gastrointestinal tract. When 50 mg of the drug is taken orally, the maximum concentration in plasma is about 1 mg/l, with repeated administration it reaches 2-3 mg/l. This exceeds the MIC for many sensitive fungi.

In blood plasma, no more than 12% of the drug is bound to proteins, the main amount is in free form. Fluconazole is very poorly metabolized by the liver and is excreted by the kidneys mainly unchanged. Excretion of the drug depends on the glomerular filtration rate.

High concentrations of fluconazole are created in the skin and nails. The hydrophilicity of fluconazole, which is in free form, allows it to quickly penetrate into the nail plate through the nail bed. Fluconazole can be detected in the nail plate just a few hours after administration. Fluconazole has some keratinophilicity and is cleared from the stratum corneum more slowly than from plasma.

For oral administration, the drug is available in the form of gelatin-coated capsules of 50, 100, 150 or 200 mg, in a package of 1, 7 or 10 capsules.

In the treatment of onychomycosis, fluconazole is used according to a pulse therapy regimen, prescribing 150 mg (once) per week. The duration of such therapy depends on the form and localization of onychomycosis: about 6 months for damage to fingernails, up to 12 months for toenails. Abroad, a pulse therapy regimen is used with the prescription of 300 mg per week (2 capsules of 150 mg each) for 9 months. Doses for children should not exceed 3-5 mg/kg per week.

The possible interaction of fluconazole with other drugs should be taken into account. Fluconazole should not be co-administered with cisapride. Fluconazole increases the half-life of hypoglycemic agents - glibenclamide, chlorpropamide, tolbutamide, potentiates the effect of indirect anticoagulants, increases the concentrations of phenytoin and cyclosporine. Rifampicin reduces fluconazole concentrations.

When prescribing fluconazole for long courses in large doses, the state of renal function is taken into account.

Side effects include nausea and abdominal discomfort. Treatment of onychomycosis with small doses of fluconazole once a week is usually not accompanied by any side effects or toxic effects.

Choice of drug

When choosing a drug for the systemic treatment of onychomycosis, you need to remember that each drug can provide a cure if given a reasonable and reasonable prescription.

We consider the spectrum of its action to be the main criterion determining the choice of a systemic drug. The spectrum should include fungi isolated from affected nails. In this regard, the etiology of onychomycosis, according to cultural studies, should be known to the doctor. If the etiology is unknown or several fungi have been isolated, a broad-spectrum drug is prescribed, including dermatophytes, Candida fungi, and non-dermatophyte mold fungi (Table 4.2.1).

Table 4.2.1

With a known etiology, the choice of drug is determined by the type of fungus isolated in the culture. For onychomycosis caused only by dermatophytes, terbinafine or griseofulvin is prescribed. For onychomycosis caused by Candida fungi and for candidal paronychia, itraconazole, ketoconazole or fluconazole are indicated. For onychomycosis caused by nondermatophyte molds, itraconazole is used.

We consider the second criterion clinical form onychomycosis, severity and localization of the lesion. Treatment of fungal infections affecting toenails with severe hyperkeratosis and matrix involvement requires prolonged treatment. In these cases, griseofulvin or ketoconazole are often ineffective and unsafe in terms of side and toxic effects. For onychomycosis of the toes, the drugs of choice are itraconazole and terbinafine.

If you still have to prescribe griseofulvin and ketoconazole, then systemic treatment They are best combined with local therapy with antifungal agents and removal of the affected nail plate. This increases the effectiveness of treatment and helps reduce its duration.

The third criterion is the safety of treatment, the risk of side and toxic effects. Security issues are discussed below.

Duration of treatment

The duration of treatment for onychomycosis depends on the rate of nail growth. The growth rate is determined by the location (toenails grow more slowly), the age of the patient and concomitant diseases- in elderly and weakened patients, people with chronic systemic diseases or previous nail pathology, they grow more slowly.

On average, healthy fingernails grow back in 4-6 months, and healthy toenails in 12-18 months. These periods determine the duration of treatment with griseofulvin and ketoconazole, as well as fluconazole.

Terbinafine and, to a greater extent, itraconazole can accumulate in the nail and remain there for a long time after treatment is discontinued. This allows you to shorten the treatment period by using short courses, intermittent therapy and pulse therapy. However, the recommended duration of treatment for such regimens is only approximate; in some cases, when toenails are affected with severe hyperkeratosis or degenerative phenomena, treatment must be extended.

Methods of prescribing drugs

There are 4 regimens for prescribing systemic drugs for onychomycosis.

1. Standard regimen, providing for daily intake usual dose drug during the entire treatment period. The duration of treatment corresponds to the time of growth of the nail plate. Any systemic drug can be prescribed according to this regimen.

2. A shortened scheme, in which the treatment period is shorter than the time of nail regrowth. Treatment is carried out with regular or increased doses. This regimen can use itraconazole and terbinafine, which can remain in the nails for a long time after stopping treatment.

3. An intermittent, or intermittent, regimen involves prescribing a regular or increased dose of the drug in several short courses. The intervals between these courses are equal to the duration of the courses themselves, for example a weekly course with a weekly interval. According to this scheme, you can use itraconazole and terbinafine, which accumulate and linger in the nails for a long time, and, in principle, all lipophilic drugs. The intermittent circuit has not yet received widespread acceptance.

4. Pulse therapy scheme. According to this scheme, an increased dose of the drug is prescribed in short courses at intervals exceeding the duration of the courses themselves. Treatment can be short, as with itraconazole, or as long as the nail plate grows out, as with fluconazole.

The most common drug regimens used throughout the world are shown in Table. 4.2.2.

Table 4.2.2

* In the practice of domestic dermatologists, it is customary to change the regimen during treatment with griseofulvin: in the 1st month, 1000 mg of the drug is prescribed every day, in the 2nd month - every other day, in the 3rd and the rest - once every 3 days.

The advantages of short, intermittent and pulse therapy regimens are their safety in terms of side and toxic effects and convenience for the patient while maintaining high efficiency. However, the standard treatment regimen with any drug gives statistically better cure rates.

Treatment safety

Security, i.e. the absence of serious side and toxic effects of the drug is one of the main requirements for any systemic therapy. First of all, it should be said that none of the antifungal agents used is free from side and toxic effects. In general, with reasonable prescription of drugs, all these side effects are transient, do not pose a threat to the life and health of the patient, and are almost always easily tolerated. Severe disorders complicating treatment with systemic drugs are very rare and are either anaphylaxis or idiosyncrasy.

According to the pharmacokinetic properties that determine the distribution and metabolism of the drug in the patient’s body, and therefore the possibility of certain side effects, all are presented in Table. 4.2.2 drugs can be divided into 2 groups. One group includes lipophilic drugs: griseofulvin, terbinafine, ketoconazole and itraconazole. They are not completely absorbed in the intestine; they are present in the blood predominantly in the form bound to plasma proteins, accumulate in tissues, undergo intensive metabolism in the liver, and are excreted in an altered form. The only representative of the other group is the hydrophilic drug fluconazole.

General pharmacokinetic properties cause some side effects common to all of these drugs.

So, suction in digestive tract All 4 lipophilic drugs may be complicated by dyspeptic symptoms: nausea, abdominal discomfort, sometimes pain, vomiting. Intensive metabolism in the liver determines the possibility of hepatotoxic effects, manifested by an increase in the concentration of liver transaminases, alkaline phosphatase. All these effects can be prevented by prescribing therapeutic doses of drugs strictly according to indications in compliance with the recommended method of use.

Fluconazole is a relatively safe drug, as evidenced by extensive experience in its use for deep mycoses. The side effects of fluconazole are also similar to those of other drugs - dyspepsia and very rare cases of toxic hepatitis. Features of the side and toxic effects of each of those included in the table. 4.2.2 antifungal agents are shown above in the description of these drugs.

It should be recognized that the risk of toxicity depends on the effectiveness of the drug. The less effective the drug is, the larger its doses have to be prescribed. The likelihood of toxic effects also depends on the characteristics of pharmacokinetics. Drugs with a high affinity for keratin, which accumulate in the nails, can be prescribed in shorter courses. The shorter the treatment period, the less likely unwanted effects.

The least dangerous regimens are pulse therapy, intermittent and shortened regimens;

the prescription of the drug must be etiologically justified. If the spectrum of action of the drug does not include the isolated pathogen, it should not be prescribed even in large doses;

the duration of treatment with traditional means can be reduced by using combination therapy or an intermittent regimen;

interactions with other drugs should be taken into account; no systemic drug should be prescribed to patients with liver disease;

No systemic drug should be prescribed during pregnancy and lactation.

Low efficiency and relatively low ability to accumulate in nails cause a greater risk of using traditional systemic agents griseofulvin and ketoconazole. These drugs are prescribed according to a standard regimen for up to 1 year, sometimes longer. The frequency of side effects and toxic effects is greatest when using griseofulvin and ketoconazole. With the advent of modern antifungal agents, neither griseofulvin nor ketoconazole is recommended for use as monotherapy for onychomycosis.

If the doctor does not have drugs other than griseofulvin or ketoconazole in his arsenal, he should consider how to make treatment with these drugs safe while maintaining effectiveness. There are two solutions to the problem. Firstly, it is possible to shorten the duration of treatment, and at the same time increase its effectiveness through combination therapy using local antifungal drugs and aids. Secondly, you can use an intermittent regimen, periodically (no longer than 1 week) allowing the patient’s body to rest and also combining systemic therapy with active local treatment.

The possibility of interaction of antifungal agents with other systemic drugs should always be considered. When prescribing a drug, you should carefully read the instructions or refer to this section of our book.

The main contraindications to systemic therapy for onychomycosis are liver disease and pregnancy. None of the systemic antifungal drugs should be prescribed to patients with liver disease or a history of hepatotoxic reactions. If persistent clinical or laboratory signs of liver dysfunction appear during treatment, treatment is discontinued.

When prescribing any drug daily for a period of more than 1 month, liver function indicators should be regularly determined - the content of aminotransferases and alkaline phosphatase (Table 4.2.3), starting with a control study before starting therapy.

If renal function is impaired or the glomerular filtration rate decreases, a dose adjustment of terbinafine may be required, since this drug is excreted primarily by the kidneys. No dose adjustment of fluconazole is required because it is prescribed in a relatively small dose only once a week.

Drug allergies, for example to penicillin antibiotics Many authors consider griseofulvin to be a contraindication.

Table 4.2.3

* When prescribing any drug, the individual characteristics of the patient, in particular his attitude to alcohol, should be taken into account. In people who regularly use alcoholic drinks, the level of liver aminotransferases is recommended to be determined after 1 week of treatment with any drug.

None of the 5 systemic drugs are recommended for pregnant women. With onychomycosis, the therapeutic benefit does not exceed the risk to the fetus. Because everything system tools excreted or can be excreted in milk, they should not be prescribed during lactation.

Drugs from the azole group can affect the metabolism of steroids in the human body. However clinical manifestations such interactions are not observed when using therapeutic doses. Doses, regimens and treatment periods used in the treatment of onychomycosis are much less than the maximum safe doses and timing recommended for azole drugs. Treatment of onychomycosis with azole drugs does not pose any risk of disrupting the patient's steroid hormone metabolism.

Reasons for failure of systemic therapy

When considering cases of unsuccessful treatment of onychomycosis with systemic antifungal drugs, it is worth paying attention to both the shortcomings of the drugs themselves, as well as their incorrect prescription by the doctor and the patient’s non-compliance with the prescribed dosage regimen.

Treatment with griseofulvin and ketoconazole is the least effective and most likely to cause side effects. Even with a treatment period of 1 year, the clinical and mycological effectiveness of treatment barely reaches 50%, and the relapse rate is 30-40%. Failure of treatment with griseofulvin or ketoconazole alone without the use of topical therapy can be considered common.

Doctor errors include prescribing potentially highly effective antifungal drugs without taking into account the clinical picture and etiology of onychomycosis, using inadequate doses and timing of treatment, ignorance individual characteristics patient (Table 4.2.4).

Failure of a patient to comply with the prescribed regimen of taking the drug is partly a mistake of the doctor, who did not explain to the patient the importance of strict adherence to this regimen and does not monitor the implementation of his recommendations.

There are cases when, even with a fully justified prescription, and the doctor and patient comply with all the rules and recommendations, it is not possible to cure onychomycosis or achieve removal of the fungus from the affected nails. In these cases, the treatment period is extended, the drug is replaced (for example, terbinafine is replaced with itraconazole and vice versa), and treatment with local antifungal agents is added to systemic therapy. In addition to prescribing antifungal agents, in the treatment of onychomycosis it is necessary to remove the affected parts of the nail in various ways (removal of the nail plate, keratolytics, cleaning the nail bed).

Table 4.2.4

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What types of treatment are carried out against nail fungus

Nail fungus is treated in different ways

Severe damage to the nail plate, when it is completely deformed, is called hypercarotic form. In this case, self-medication is unacceptable. In other cases, you can get by with ointments, creams and sprays based on some multifungal active ingredient.

Most often, therapy includes:

• Oral antifungal medications plus application similar drug to the site of the lesion.
• Removal of the affected part of the nail plate using keratolytic plasters Ureaplast, Microspora, Onychoplast, followed by treatment with antifungal drugs. Removing part or all of the plate speeds up the process of treatment and restoration of the nail.
• Application of antifungal varnishes. Helps in complex treatment, as a prophylactic agent or at the very initial stage of the disease. Trade names of varnishes: Amorolfine (Amorolfine), Lotseril (active ingredient amorolfine), Ciclopirox, Batrafen (on ciclopirox), Omorolfine.
• Application of creams, ointments, solutions and sprays based on terbinafine.
• Prescription of oral systemic antifungal drugs - Griseofulvin, Grimelan, Ketoconazole, Itraconazole, Irunin, Terbinafine, Fluconazole and others. At the same time as the tablets, external agents are prescribed depending on the nature of the disease.
• In severe cases of the disease, medications are prescribed that contain not only antifungal substances, but also antibacterial or corticosteroid components. For example, Travocort contains isoconazole for fungi and diflucortolone valerate (corticosteroid), which relieves itching and allergies. Pimafucort is also a good drug, which contains a broad-spectrum antibiotic, an antifungal drug and a corticosteroid.
• As maintenance therapy, lotions with Dimexide are prescribed - it relieves inflammatory processes, drops and ointments with zinc, copper - accelerate the restoration of skin and nails.

Terbinafine in tablet form

One of the most affordable means for oral, that is, external, administration for nail fungus is Terbinafine. The name of the drug and the active substance are the same. Also suitable for treating skin, hair, mucous membranes. It is available in the form of ointments, creams, tablets, sprays, and solutions. It is rarely prescribed systemically; in most cases, local application is indicated. Belongs to the group of allylamines.

Terbinafine has a strong fungicidal effect on various types dermatophytes and other fungi and yeasts. It destroys intercellular membranes, and over time the fungi die. This drug is prescribed for a number of diseases: nail fungus, microsporia, mycoses caused by the fungus rubrum, trichophytosis, candidiasis of the mucous membranes and skin.

For local treatment of fungus, Terbinafine cream, ointment or spray is prescribed once a day. The approximate duration of the course is 1 week. You cannot interrupt the course, despite the fact that improvement will occur after the second or third use of the drug. The main contraindications to the use of drugs with this active substance are liver and kidney failure, as well as tumors of various natures, psoriasis, and endocrine diseases.

It is most convenient to use sprays from different manufacturers. Alcohol solutions terbinafine are quickly absorbed into the nail plate, practically do not enter the blood (less than 5%), and dry instantly. So you can put on socks and shoes almost immediately after application.

Preparations for the treatment of mycoses with this active ingredient:

• Lamisil.
• Binafin.
• Thermikon.
• Terbasil.
• Fungoterbin.
• Exifin.
• Atifin and others.

They all have the same active ingredient, the same concentration for specific forms. Only the auxiliary substances that are responsible for softening the plate and transporting the active substances into the nail differ. It is worth choosing based on individual tolerance and price.

Itraconazole tablets

This is another drug for the treatment of fungus with a broad spectrum of action. Belongs to the group of triazoles. Itraconazole has also been used successfully to treat lesions of the nail plate, as has Terbinafine. However, it is prescribed with caution to patients with liver and kidney disease.

Names of drugs based on Itraconazole:

• Orungal.
• Tecnazole.
• Orungamin.
• Orunite.
• Rumicosis and others.

The most affordable are Irunin capsules. The duration and course of treatment (with intervals between doses) are prescribed by the doctor strictly individually.

Fluconazole in tablet form

It also belongs to the triazole series of drugs, that is, it acts similarly to Itraconazole. Its advantage over related drugs is that it has virtually no effect on human pathogenic microflora, that is, beneficial fungi in our body.

This is a relatively expensive drug that is prescribed in in rare cases when the patient has difficulties with immune system. So, he can be prescribed if there are tumors, immune depression, if the patient is going to undergo surgery or radiation therapy in the near future. In common cases of nail fungus, Fluconazole is not recommended. It is worth noting that this drug has a number of unpleasant side reactions that are not characteristic of other antifungal agents.

Analogues:

• Diflucan.
• Mikosist.
• Flucostat.

All these capsule preparations are focused mainly on the systemic treatment of fungal diseases associated with the human genitourinary system.

Ketoconazole in tablet form

A fairly active antifungal drug that is most effective in the treatment of systemic lesions. There are practically no contraindications - only intolerance, pregnancy, lactation, serious illnesses liver, however, it can cause a number of side effects.

Medicines containing Ketoconazole:

• Fungikok.
• Oronazole.
• Dermazol.

This active substance is also often used in the production of medicinal and cosmetic shampoos and ointments. For example, it is found in Nizoral shampoo and Perhotal.

Video: Antifungal drugs

Let's summarize the main drugs for nail fungus

At the slightest suspicion of nail fungus, immediately go to the doctor

Modern pharmacology can offer a number of antifungal drugs that affect many types of microfungi. Some of the drugs can be classified as specialized for the treatment of certain groups of diseases. For example, drugs based on Ketoconazole or Fluconazole act.

Most often, mycologists prescribe products based on Terbinafine or Itraconazole to treat nail fungus. Some of the drugs based on them are widely advertised and are quite expensive. At the same time, the effect of such popular drugs has been well studied, which allows doctors to recommend these particular medications.

If the problem has not gone too far, you can try to self-medicate. To do this, you need to soften the damaged part of the plate using special patches and remove it. Then choose an ointment, cream or spray for topical use based on Terbinafine or Itraconazole and use according to the instructions.

To eliminate unpleasant sensations, ointments with corticosteroids are suitable. Zinc and copper ointments will contribute to skin restoration. If therapy does not produce results, contacting a doctor is necessary. Not only loss of the nail is possible, but also systemic damage to the body by fungi.

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Itraconazole: brief description

Itraconazole is an antifungal agent classified as azole derivative with systemic action. It has two dosage forms: capsules and solution. The active ingredient is itraconazole.

Indications for use

It is advisable to use Itraconazole for the treatment skin from various fungal infections and inflammatory processes.

In addition, it is effective for:

• dermatoses;
• candidiasis;
• lichen planus;
• mycotic eczema (when large areas of skin are affected);
• dermatophytosis;
• sporotrichosis;
• onychomycosis.

Side effects

In general, Itraconazole was well tolerated by patients, but in some it provoked:

• failure in the functionality of the gastrointestinal tract;
• increased blood pressure;
• deterioration of hair condition, hair loss;
• decreased sexual activity;
• fatigue;
• headaches and vertigo;
• skin rashes, itching and burning;
• swelling of the face and limbs.

Features of application

Itraconazole is taken orally. It is better to drink capsules before eating, and the solution after eating. Daily norm and the duration of the therapeutic course is determined by the attending physician.

Fluconazole: a brief description

The drug has the same name active ingredient. Produced by domestic and foreign pharmaceutical companies. It has two dosage forms: capsules and suspension. Designed for oral use. Popular analogues of Fluconazole: Terbinafine, Pimafucin, Nystatin and Itraconazole. Only a qualified specialist should decide whether it is possible to take Itraconazole instead of Fluconazole, or replace the latter with another analogue.

Side effects and overdose

Some women noted that Fluconazole therapy was accompanied by:

• allergic manifestations: erythema, rashes on the epithelium, urticaria and swelling;
• severe pain in the head;
• convulsive lesions of the limbs;
• dizziness;
• taste bud disorders;
• diarrhea;
• nausea and vomiting;
• impaired functionality of the kidneys and liver.

If you take a large dose of Fluconazole, it can cause hallucinations and paranoia.

Is it possible to combine

Since these two drugs belong to the same pharmaceutical group, many patients wonder whether it is possible to take Fluconazole and Itraconazole at the same time? Doctors say no, explaining that such a combination can provoke the development of side effects and negatively affect the patient’s health.

What to choose

Comparing Itraconazole and Fluconazole, one can initially note that the difference between the drugs lies in the price: the first will cost the patient 390-460 rubles, the second - only 35-55 rubles. Both drugs have broad action and fungicidal properties. They should not be taken during pregnancy or while breastfeeding, but they both rarely cause side effects.

If the patient suffers from acute thrush, but the disease was diagnosed on time; all she needed to do was take one Fluconazole tablet. Itraconazole in a similar situation should be taken for a week. If we compare drugs in the fight against chronic thrush, then the use of Fluconazole is carried out according to the scheme once every 72 hours for nine days, and Itraconazole should be used once a day for 5-7 days.

Only the attending physician should decide which of these two drugs is best for the patient, based on the diagnostic results.

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Maria Vladimirovna asks:

What should I do if, after treatment, symptoms of genital candidiasis reappear?

If symptoms candidiasis genital organs in adults return after treatment, it is recommended to consult a doctor again. The smear should be re-analyzed for the presence of fungus and its concentration should be determined.

A smear is taken during a gynecological examination. Next, it is examined under a microscope for the presence of fungus. If in the analysis increased concentration Candida fungus, this indicates that the person has re-developed candidiasis. This test is necessary to exclude other diseases similar to candidiasis ( for example, bacterial vaginosis).

The doctor may also prescribe additional tests to identify the cause that contributed to the return of candidiasis.

These tests may be:

• biochemical blood test with determination of glucose concentration;
• bacteriological culture of a smear.

Biochemical blood test with determination of glucose concentration.

One of the most common reasons re-development of candidiasis is diabetes mellitus. This pathology is characterized by impaired glucose metabolism, as a result of which its level increases in tissues and blood. Therefore, first of all, it is necessary to determine the glucose concentration in order to predetermine further treatment tactics for candidiasis.

PCR analysis of smears for infections.

Genital infections in 20 percent of cases accompany the development of genital candidiasis. Often, chronic infections of the genital organs are the cause of the re-development of candidiasis. Therefore, it is very important to calculate the presence of infections in the body.
Polymerase chain reaction ( PCR) is one of the most accurate methods in the diagnosis of genital infections. PCR determines the genetic material of pathogenic bacteria and viruses in the material being tested.

This method is indispensable in the diagnosis of infections such as:

Bacteriological culture of a smear.

This test is necessary to identify types of Candida fungus. It is known that 80 percent of candidiasis is caused by the fungus Candida Albicans.

But there are more than 100 types of Candida fungus that can cause recurrent candidiasis:

• Candida Atlantica;
• Candida Antarctica;
• Candida Maltosa;
• Candida Crusei;
• Candida Tropicalis;
• Candida Glabrata and others.

The standard microscopy smear test, which is performed in the diagnosis of candidiasis, does not detect the type of fungus. Therefore, if genital candidiasis develops again, it is necessary to conduct a bacteriological culture of the smear. It consists of inoculating the test material on special media on which the fungus grows and forms colonies. Each type of fungus forms its own specific colony, which is determined by a laboratory technician. This method is long-term, but it is necessary for the re-development of candidiasis.

Only after identifying the cause of the re-development of genital candidiasis should treatment begin. If candidiasis develops again, longer treatment is required. So, if with the initial development of candidiasis, treatment with antifungal drugs lasts from 3 to 6 days, then with its repeated development, the duration of treatment is from 10 to 20 days. Local preparations ( suppositories, ointments) are supplemented with tablets for oral administration.

The following combinations of drugs are used:

• fluconazole tablets + terzhinan suppositories;
• Fluconazole tablets + Livarol suppositories;
• itraconazole capsules + zalain suppositories.

Fluconazole + terzhinan.

If candidiasis recurs, single use of fluconazole is not recommended. Instead, the drug is prescribed monthly for six months. A 150-milligram fluconazole tablet is taken once a month for six months. At the same time, Terzhinan suppositories are prescribed, one suppository for 10 to 20 days ( depending on how many times candidiasis recurred). Treatment should not be interrupted even during menstruation.

Fluconazole + livarol.

Livarol candles ( the active substance of which is ketoconazole) in combination with fluconazole is used in cases where candidiasis has recurred several times ( more than 3 – 4 times). One suppository is used for 10 days simultaneously with fluconazole 150 milligrams. A fluconazole tablet is prescribed once a week for a month.

Itraconazole + zalain.

If candidiasis develops again, itraconazole capsules 200 milligrams are prescribed for 3 days. Zalain suppositories are prescribed at the same time. If candidiasis recurs once, then the suppository is administered once. If it was repeated more than twice, then zalain is prescribed once a week for two weeks.

The treatment prescribed by the doctor must be followed throughout the entire period. You should not abandon treatment if the symptoms of candidiasis have disappeared. Most often, it is the interruption of treatment that causes the re-development of genital candidiasis.

Also prescribed are washings and baths with a decoction of chamomile or oak bark. For this, a tablespoon of oak bark ( or two teaspoons of chamomile flowers) fill with 250 milliliters ( glass) water and heat in a water bath for 30 minutes. Next, the broth is filtered and used for toileting the external genitalia. Or make the required amount of decoction at the rate of a tablespoon per glass of water, and pour it into a basin ( bath), where the woman sits. The procedure lasts 15 – 20 minutes.

Treatment of the entire couple, and not just the partner, plays an important role in preventing the re-development of candidiasis. After all, a sexual partner can be a constant source of infection without realizing it.