Itraconazole: instructions for use. "Itraconazole": instructions, cheap analogues, reviews and release form

Capsules "Itraconazole" are intended for the treatment of mycoses on the body. They contain in their composition the optimal dose of the active substance, which inhibits the activity and reproduction of pathogenic microorganisms. Since the drug has contraindications and side effects, it should be taken strictly according to the instructions and only as prescribed by the doctor.

The drug has the same name as the active substance

The antimycotic drug is available in the form of capsules. They have a hard gelatinous shell. The color of the medicine case depends on its manufacturer. Tablets are packaged in several pieces in blisters with cells.

The active ingredient of the drug is a substance with the same name. Itraconazole is contained in the preparation in an amount of 100 mg. The composition of auxiliary components depends on its manufacturer. Information about this is given in the table.

FROM detailed composition"Itraconazole" can be found if you study the instructions attached to the capsules.

Pharmacological properties

When appointed medicinal product the physician must tell the patient about its action and effect on the body, that is, explain to the patient in an accessible language pharmacological properties prescribed medication.

Pharmacodynamics

Pharmaceutical preparation is a derivative mass of the substance triazole, which exhibits the functions of an antimycotic agent capable of inhibiting the biosynthesis of a pathogen cell membrane component. She, in turn, takes an active part in maintaining the integrity of these elements. Therefore, a violation of its work leads to the destruction of the fungus by increasing the permeability of membranes, as well as changes in cell lysis.

Active ingredient medication is effective in relation to various infectious diseases caused by fungal microflora. It copes with yeast-like pathogens, dermatophytes and rarer pathogens.

Pathogenic microorganisms can develop resistance to such substances. But this process is extremely slow. Its cause lies in the presence of certain genetic mutations.

Pharmacokinetics

With long-term use of the drug, it active substance will accumulate in plasma. The maximum concentration of this component of the drug under the curve, which also includes the time indicator, is 4-7 times higher when compared with the concentration after a single application. The equilibrium value of this parameter is observed for 15 days.

After the patient stops taking the drug, the plasma concentration of the active substance drops to an undetectable value. This process continues for 4-7 days. It all depends on the dosage of the drug "Itraconazole" and the duration of the therapeutic course.

The final half-life of the drug is limited to 16-28 hours with a single dose of a pharmaceutical drug and 34-42 hours with repeated treatment with capsules.

The active components of "Itraconazole" very quickly go through the process of absorption after ingestion. The absolute bioavailability of the drug is not more than 55%. Maximum rate this parameter can be observed in the case of taking capsules after meals.

Main component medical composition binds to plasma proteins. This figure is usually in the range of 99.8%. The affinity of the component for lipids will also be noted.

According to laboratory studies, about 35% of the active substance "Itraconazole" is excreted from the human body through the kidneys in the form of inactive metabolites. 54% of the component exit through the intestines.

The drug is excreted from the body mainly through the intestines and to a lesser extent through the kidneys.

Indications for use

The drug in the form of capsules, as well as other drugs that contain Intraconazole (ointment, suppositories or cream), is effective in combating fungal infections. Specialists prescribe this remedy to their patients after they diagnose the following disorders in them:

• Candidiasis of the vulvovaginal type;
• Mycosis of the skin;
• Mycosis of the eyes and oral cavity;
• Onychomycosis;
• Systemic types of mycosis (blastomycosis, histoplasmosis, systemic aspergillosis, candidiasis and others);
• Tropical mycoses.

To verify the effectiveness of the drug in the fight against a particular disease, you should study its description, as well as analyze the sensitivity of the pathogen to the active component of the drug.

Instructions for use

"Itraconazole" capsules are intended for oral administration. They should be swallowed whole. The procedure is best done after a meal.

The dosage of the drug and the duration of therapy depend on a number of factors. First of all, attention is drawn to the fact in the treatment of which disease the patient should take this medication.

In certain diseases, patients with reduced immunity need individual adjustment of the optimal dosage. This need often arises in patients with AIDS, neutropenia, or those who have undergone transplantation. internal organs. This feature is associated with the likelihood of reducing the bioavailability of the drug. That is why it may be necessary to increase the dose of Itraconazole.

You can see the first results that show the effect of the drug approximately 2-4 weeks after it was used for medicinal purposes.

Use during pregnancy and lactation

Allows the intake of Itraconazole capsules by women who are carrying a child. Such treatment is justified in systemic mycoses and only if the potential benefit of therapy outweighs the potential risk to fetal health.

If the medicine is taken by a woman of childbearing age, then she is recommended to use contraceptives without fail at the time of intimacy with a man.

If "Itraconazole" is prescribed to a breastfeeding woman, then the issue of temporarily stopping this process is additionally considered in order to ensure the safety of the baby. This information contains instructions for the use of the drug.

According to experimental research it was found that taking this medication by pregnant women can lead to the development of abnormalities in the fetus.

During pregnancy, the drug is allowed only as a last resort.

Application for violations of the liver

Doctors strongly recommend that patients with impaired liver function refuse to take Itraconazole. However, such therapy is allowed for patients diagnosed with cirrhosis of the liver. In this case, the capsules should be taken under full control the attending physician. Additionally, you will need to regularly check the level of the active substance of the drug in the blood plasma. Upon receipt of unsatisfactory test results, it is necessary to correct the dosage of Itraconazole.

If the doctor reveals an increased activity of liver transaminase, the drug will be prescribed to the patient only if the expected benefit from the therapeutic course is higher than the risk to human health, since such treatment can lead to even more damage to the internal organ.

If treatment with Itraconazole is required for more than 1 month, then the doctor will periodically refer the patient to the liver for examination. In the event that diseases of this organ occur during treatment, the medicine is immediately canceled.

Use for disorders of the kidneys

If the patient has been found to have disorders that do not allow the kidneys to function properly, then his treatment with Itraconazole should be carried out under the full control of the function of these organs. If the test results are negative, it may be necessary to adjust the initial dose of the drug.

Use in children

At the moment, drug manufacturers do not have enough data to talk about the safety of taking Itraconazole by children.

The safety of the drug for the child's body has not been proven

Side effects

Intraconazole may cause side effects. This is evidenced by the reviews of patients who underwent treatment of a fungal infection with it.

These are not the only side effects that patients develop due to taking this medication. They may also experience edematous syndrome and hyperthermia.

Nausea and skin rash are the most common side effects.

Contraindications

This remedy can not treat the fungus for all patients. The drug is prohibited for use by men and women who have the following contraindications to it:

1. fructose intolerance;
2. Lack of isomaltose/sucrose;
3. Chronic form of heart failure;
4. Pregnancy and lactation;
5. Need for oral midazolam, nisoldipine, or triazolam;
6. Hypersensitivity of the body to the active substance of the drug or its auxiliary components.

Separately, there are relative contraindications to taking Itraconazole. These include the following states:

1. Childhood and old age;
2. Hypersensitivity to different drugs, which belong to the group of azoles;
3. Severe forms of impaired renal and hepatic function.

It is strongly recommended to refuse treatment with this drug for patients who are forced to take drugs that can change the concentration of the active substance "Itraconazole" in the blood.

special instructions

Capsules are not prescribed to patients who have been diagnosed with symptoms of disruption of the digestive tract. The same applies to patients with a history of congestive heart failure.

The drug is not suitable for patients who have problems in the liver. Only in rare cases is it possible to treat patients with diseases of this organ with Itraconazole. In such a situation, it is necessary to constantly monitor the functioning of the liver and the condition of the person.

In the case of an increase in the level of liver transaminase activity, the drug is prescribed only when the potential benefit of therapy outweighs the potential risk of harm to the patient's health.

Withdrawal of the drug is mandatory if, during the course of the drug course, the patient develops symptoms of liver dysfunction, heart failure, or peripheral neuropathy.

In the presence of diseases of the internal organs, monitoring of indicators is required during the period of taking Itraconazole

drug interaction

When drawing up a treatment regimen, the doctor takes into account the drug interaction of Itraconazole with other medicines. Attention is drawn to the following points:

• Drugs that can reduce acidity gastric juice may reduce absorption active component"Itraconazole";
• Excessively reduce the bioavailability of the drug inducers of the CYP3A4 isoenzyme. As a result, its effectiveness in the treatment of fungal infection is greatly reduced;
• An increase in the bioavailability of the drug is carried out by powerful inhibitors of the CYP3A4 isoenzyme;
• The drug has the ability to inhibit the metabolism of a number of drugs, which are cleaved by the CYP3A4 isoenzyme. The result of this influence is to increase their effect. This increases not only the usefulness of drugs, but also their harmfulness to the body.

The physician should carefully monitor the condition of the patient to whom this antifungal drug has been prescribed, if he has to take other medicines at the same time. Namely:

1. Medications of the glucocorticosteroid group;
2. Anticoagulants of indirect type;
3. HIV protease inhibitors;
4. Blockers of slow calcium channels;
5. HMG-CoA reductase inhibitors, which tend to break down under the influence of the CYP3A4 enzyme;
6. drugs of the immunosuppressive group;
7. Antitumor agents.

A specialist who observes the course of a fungal disease in a patient should take into account the drug interaction of Itraconazole. This point should by no means be overlooked. Neglect of this rule can have a number of unpleasant consequences for the patient. In addition, it causes a decrease in efficiency. drug treatment and increased activity of the infectious agent.

Analogues

There are many drugs from different manufacturers with the same active substance.

"Itraconazole" has various analogues. If necessary, they can replace this drug. Most often, such a need arises if the patient after taking the medication has severe side effects or has contraindications to it. Also, some analogues of "Itraconazole" have a lower cost, which attracts the attention of the patient.

Substitutes for this antifungal drug include:

1. "Eszol";
2. "Itrakon";
3. "Irunin";
4. "Itrazol";
5. "Orungal";
6. "Mikokur";
7. Trioxal.

In no case should you try to replace the drug prescribed by your doctor with its analogue on your own. Such actions can significantly reduce the effectiveness of the therapeutic course against a fungal infection and cause a number of negative reactions from different body systems. Such questions should be discussed with a specialist. Only he decides whether it is possible to replace Itraconazole or not.

Price and points of sale

The medicine can be found on sale in many pharmacies. The price of the drug "Itraconazole" is in the range of 335-485 rubles per 1 package. This medication is available on prescription from a doctor.

Solution or capsules) is used to treat various fungal infections. At the same time, it is equally effective for the treatment of diseases localized in different parts of the body.

medicinal substance

The drug itself and any analogue of "Itrakanozol" belongs to the class of antifungal triazoles. This artificially synthesized drug prevents the synthesis of ergosterol, which is necessary for the normal functioning of fungi. The drug "Itraconazole" inhibits the development of dermatophytes, Candida, mold fungi and other pathogens. Some strains of microorganisms are resistant to this tool.

The drug "Itraconazole" is available in tablets, capsules, in the form of an ointment. There are far more than one analogue of Itraconazole on sale. Such drugs are available in different dosage forms.

Any analogue of "Itraconazole" and, in fact, this drug itself is most often used for the treatment of fungal infections of the respiratory system, in particular the lungs. These medicines are also used to treat patients who have fungal infections in the throat, mouth or esophagus. Very often, this infection affects the nails of a person. In this case, another dosage form of the drug "Itraconazole" is used - an ointment for external use, which effectively fights a fungal infection on the nails or skin. It is also prescribed for psoriasis.

Indications for use

This drug and its analogues are used for the following diseases:

Dermatomycosis;

Candidiasis;

Sporotrichosis;

versicolor;

Onychomycosis;

Blastomycosis;

Cryptococcosis;

Keratomycosis;

Paracoccidioidomycosis;

Systemic aspergillosis and candidiasis;

Histoplasmosis;

Tropical mycosis.

The duration of therapy may be adjusted depending on clinical picture. Most often, this drug is taken once a day. The most commonly used treatment regimens:

Pityriasis versicolor: within a week, 200 mg;

Dermatomycosis: during the week, 200 mg or 100 mg for 15 days;

Onychomycosis: 3 months at 200 mg or a week at 200 mg / 2 times a day;

Dermatophytosis of the hands and feet: a week of 200 mg or 100 mg for 1 month;

Candidiasis: within 15 days, 100 mg;

Keratomycosis: within 3 weeks, 200 mg.

Methods of administration for lung infections

For Therapy respiratory tract appoint tablets or capsules "Itraconazole". Analogues are cheaper, but they may have a more distant effect in time, so the disease is more difficult to defeat in the shortest possible time. Tablets or capsules are taken 1-2 times a day, during or immediately after meals. It usually takes at least 3 months to treat a fungal lung infection. In some cases, the doctor may prescribe the following course of therapy: 3 tablets per day for 3 days, and then 3 months, 1-2 tablets per day.

Taking medication for nail infections

The drug "Itraconazole" - tablets that are also prescribed for the treatment of fungal nail infections. For a complete cure, it is taken 1 time per day for 12 weeks. More effective is the oral solution "Itraconazole". It is taken for 1-4 weeks 1-2 times a day. At the same time, for faster absorption, the medicine is consumed on an empty stomach. Only the attending physician is able to choose the most optimal regimen for taking the drug or prescribe an analogue of Itraconazole, who will take into account the severity of the disease and general state patient. In especially advanced cases, for the treatment of fungal infections of the nails, another form of the drug "Itraconazole" is used - an ointment that is applied to the affected areas 1-2 times a day.

Other options for using the drug

Any analogue of "Itraconazole" and this drug itself in last years increasingly used in complex therapy various types fungal infections in patients affected by HIV and AIDS. In this case, self-medication is unacceptable, since only the attending physician can correctly assess the patient's health status and the possible risks of taking Itraconazole.

special instructions

The drug "Itraconazole", analogues of this medication should be taken in accordance with the instructions and recommendations of the attending physician. In smaller or larger doses, they may be ineffective or may harm the health of the patient.

Itraconazole capsules, cheap or expensive analogues are taken as follows: capsules and tablets are swallowed whole. However, they should not be chewed or crushed. With a decrease in the level of acidity in the stomach, caused, for example, by cystic fibrosis, this should be reported to the attending physician.

In some cases, the regimen for taking this drug may be changed. Most often this happens when the patient takes the following drugs during therapy: Famotidine, Nizatidine, Esomeprazole, Cimetidine, Omeprazole, Ranitidine, Lansoprazole, Pantoprazole, " Rabeprazole.

Contraindications

In some cases, Itraconazole is contraindicated for patients. Instructions for similar drugs often prohibit the use of such antifungal drugs in case of allergies to their components. That is why, when prescribing therapy using these drugs, the attending physician must know for sure whether the patient has an allergic reaction to the substances that make up them.

The drug should not be taken by pregnant and lactating women. To prevent possible pregnancy during treatment, it is necessary to use effective means contraception. With caution, this drug is prescribed to elderly patients. Taking it in childhood is possible only if the benefit outweighs the potential risk. The drug is not recommended for patients with heart failure, ischemia, severe lung disease, renal failure.

"Itraconazole", analogues of the drug should not be taken in a double dose with a possible skipping of the medication. It is best to forget about the missed dose and continue to follow the regimen. An overdose of this drug or its analogues should not be allowed, as this can lead to very serious complications with health.

Interaction with other drugs

Before taking Itraconazole, the attending physician should be aware of which drugs the patient has taken before. This is especially true for the use of drugs such as Efavirenz, Everolimus, Sildenafil, Aliskiren, Rifabutin, Apixaban, Nevirapin, Dasatinib, Ibrutinib, Salmeterol, Darifenacin, Nilotinib, Carbazepine, Sunitinib, Colchicine, Rivaroxaban, Phenobarbital, Tamsulosin, Isoniazid, Phenytoin, Vardenafil, Rifampicin, Nevirapine , Temsirolimus.

In addition to the above drugs, before using Itraconazole, you should inform your doctor about taking the following drugs:

Anticoagulants;

antibiotics;

HIV protease inhibitors;

vitamins;

Food additives (BAA).

With the simultaneous use of "Itraconazole" and antacids, the latter are used 1 hour before or a couple of hours after taking an antifungal medication.

Side effects

The drug "Itraconazole" sometimes causes dizziness and blurred vision in the form of a split image. Do not drive or operate machinery while taking this medicine. To the most frequently mentioned side effects when taken, it includes bloating, increased gas formation, diarrhea, constipation, heartburn, the occurrence of an unpleasant aftertaste in the mouth; increased sweating, dizziness, headache, bleeding and tenderness of the gums, muscle pain, decreased muscle tone, runny nose, fever, joint pain, depression, decreased libido, hair loss.

The following side effects are considered especially dangerous for the patient's health: double vision, nausea, vomiting, abdominal cramps, heart failure, hepatitis, involuntary urination, anaphylactic and allergic reactions, dark urine, ringing in the ears, hearing loss, loss of appetite, excessive fatigue, yellowing skin and eye, numbness and tingling of soft tissues and skin, photophobia, skin rash, itching, hoarseness, pulmonary edema, impaired menstrual cycle, swelling in the face, throat, hands, ankles. If you experience any of the above symptoms, you should immediately inform your doctor.

How to choose an analogue of "Itraconazole"

Every year more and more people are faced with the problem of fungal diseases. At the same time, many patients decide that it is not necessary to purchase Itraconazole for their treatment. Analogues are cheaper, so they are often preferred. In fact, the choice of this drug or its analogues should be decided only by the attending physician. In some particularly severe cases, the complete recovery of the patient helps to achieve only Itraconazole. Analogues are cheap, but not all of them are as effective as this drug.

What can replace "Itraconazole"? Ointment, analogues of this remedy in other dosage forms are widely represented in pharmacies. Structural analogues include the following medicines produced in capsule feed: Irunin, Intramikol, Itrazol, Mikonikhol, Kanditral, Kanazol, Teknazol, Orungal, Rumikoz, Orungamine ”,“ Orunit ”.

Analogues of "Itraconazole" for therapeutic action are the following drugs:

• capsules: Diflucan, Diflazon, Itrazol, Orungal, Rumikoz, Flucostat, Fluconazole, Fungolon;
• tablets: "Atifin", "Binafin", "Ketoconazole", "Fungoterbin", "Exifin", "Nizoral";
• ointments, creams, gels: Akriderm, Lamisil Dermagel, Terbizil, Exifin, Mycomax, Mycozoral, Triderm, Fungoterbin, Ketoconazole, Canison, Lamitel , Candide, Amiklon, Zalain, Canizon, Atifin, Clotrimazole, Lamisil, Ifenek, Lamitel, Terbix, Imidil;
• candles, vaginal tablets: "Zalain", "Candide", "Canison", "Mikogal", "Imidil".

Description

Hard gelatin capsules, cylindrical shape with hemispherical ends, with body blue color and blue lid.

Compound

Each capsule contains:

active substance: itraconazole (in the form of pellets 22%) -100 mg;

Excipients: copolymer of butyl methacrylate, 2-dimethylaminoethyl methacrylate and methyl methacrylate, hypromellose, sugar pellets (sucrose, corn starch, povidone, purified water), polyethylene glycol.

Compositionav hard gelatin capsules: carmoisine (azorubine) (E122), Ponceau 4R (E124), patent blue V (E 131), brilliant black PN (E 151), titanium dioxide (E 171), gelatin.

Pharmacotherapeutic group

Antifungal agents for systemic use. Triazole derivatives. ATX code J02AC02.

Indications for use

Damage to the skin and mucous membranes:

Vulvovaginal candidiasis; pityriasis versicolor; dermatomycosis; candidiasis of the oral mucosa; fungal keratitis.

Onychomycosis caused by dermatophytes and / or yeast-like fungi.

Systemic mycoses:

Systemic aspergillosis and candidiasis; cryptococcosis (including cryptococcal meningitis): in immunocompromised patients and in all patients with cryptococcosis of the central nervous system Itraconazole should only be used if medicines first-line treatments are not applicable in this case or are not effective; histoplasmosis; blastomycosis; sporotrichosis; paracoccidioidomycosis; other rare systemic or tropical mycoses.

Dosage and administration

For optimal absorption, Itraconazole should be taken immediately after a meal. Capsules should be swallowed whole.

Elimination of the drug Itraconazole from the skin and nail tissue is slower than from plasma. Thus, optimal clinical and mycological effects are achieved 2-4 weeks after the end of treatment for skin infections and 6-9 months after the end of treatment for nail infections.

The duration of treatment may be adjusted depending on the effectiveness of the treatment.

Special patient groups

Children

Data on the use of itraconazole in children are limited. The use of Itraconazole in children is not recommended unless the expected benefit outweighs the potential risk.

Elderly patients

Data on the use of itraconazole in the treatment of elderly patients are limited. It is recommended to use the drug Itraconazole for the treatment of patients in this category only if the expected benefit from the treatment outweighs the potential risks. When choosing a dose of a drug for the treatment of elderly patients, it is recommended to take into account the decrease in liver, kidney and heart function, which are more common in the elderly, as well as the presence of concomitant diseases or the use of other drugs.

Liver dysfunction

There are limited data on the use of oral itraconazole in patients with hepatic impairment. The drug should be used with caution in this category of patients.

Kidney dysfunction

There are limited data on the use of oral itraconazole in patients with impaired renal function. In some patients with renal insufficiency, itraconazole exposure may be reduced. The drug should be prescribed with caution in this category of patients, in some cases it may be necessary to change the dose of the drug.

If you have any doubts or questions, please contact your doctor.

Security Profile Summary

The most frequent side effects reported with itraconazole in clinical trials and/or spontaneous reports are headache, abdominal pain and nausea. The most severe adverse reactions were serious allergic reactions, heart failure/congestive heart failure/pulmonary edema, pancreatitis, serious hepatotoxicity (including several cases of fatal acute liver failure), and serious skin reactions. The "Precautions" section contains Additional Information about other serious effects.

List adverse reactions

Side effects drugs are systematized with respect to each of the organ systems, depending on the frequency of occurrence, using the following classification: very often - ≥ 1/10; often - ≥ 1/100,

Infections and infestations: infrequently - infections of the upper respiratory tract, sinusitis, rhinitis.

From the blood and lymphatic system: rarely - leukopenia.

From the side immune system: infrequently - hypersensitivity; rarely - angioedema, anaphylactic reactions, serum sickness.

From the side of metabolism and nutrition: rarely - hypertriglyceridemia.

From the nervous system: often - headache; rarely - paresthesia, hypoesthesia, dysgeusia.

From the side of the organ of vision: rarely - visual disturbances (including blurred vision, diplopia).

On the part of the organ of hearing and labyrinth disorders: rarely - ringing in the ears, temporary or permanent hearing loss.

From the side of the heart: rarely - congestive heart failure.

From the side respiratory system, bodies chest and mediastinum: rarely - shortness of breath.

From the gastrointestinal tract: often - abdominal pain, nausea; infrequently - vomiting, dyspepsia, diarrhea, constipation, flatulence; rarely - pancreatitis.

From the side of the liver and biliary tract: infrequently - impaired liver function; rarely - serious hepatotoxicity (including isolated cases of fatal acute liver failure), hyperbilirubinemia.

From the skin and subcutaneous tissues: infrequently - rash, urticaria, itching; rarely - toxic epidermal necrolysis, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, erythema multiforme, exfoliative dermatitis, leukocytoclastic vasculitis, alopecia, photosensitivity.

From the side of the musculoskeletal and connective tissue: very rarely - myalgia, artpalgia.

From the side of the kidneys and urinary tract: rarely - pollakiuria.

From the genitals and mammary gland: infrequently - menstrual disorders; rarely - erectile dysfunction.

General disorders: rarely - swelling.

Laboratory research", rarely - an increase in the level of phosphokinase in the blood.

Description of individual adverse reactions

Blood and lymphatic system disorders: granulocytopenia, thrombocytopenia. Immune system disorders, anaphylactoid reaction.

Metabolic and nutritional disorders: hyperglycemia, hyperkalemia, hypokalemia, hypomagnesemia.

Mental disorders: confusion.

Nervous system disorders: peripheral neuropathy, dizziness, drowsiness, tremor.

Heart disorders: heart failure, left ventricular failure, tachycardia.

Vascular disorders: hypertension, hypotension.

Respiratory, thoracic and mediastinal disorders: pulmonary edema, dysphonia, cough.

Gastrointestinal disorders: gastrointestinal disorders.

Liver and biliary tract disorders: liver failure, hepatitis, jaundice.

Skin and subcutaneous tissue disorders: erythematous rash, hyperhidrosis.

Musculoskeletal and connective tissue disorders: myalgia, arthralgia.

Renal and urinary tract disorders: kidney failure, urinary incontinence.

General disorders: general edema, swelling of the face, chest pain, fever, pain, fatigue, chills. Laboratory research: increased levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, urea, γ-glutamyl transferase, liver enzymes in the blood; deviations from the norm of urine tests.

In the event of adverse reactions, including those not listed in this leaflet, you must stop taking the drug and consult a doctor.

Contraindications

Hypersensitivity to itraconazole or any other component of the drug; Simultaneous use of drugs-substrates of the CYP3A4 isoenzyme (see the section "Interaction with other drugs") such as levacetylmethadone, methadone; disopyramide, dofetilide, dronedarone, quinidine; halofantrine; astemizole, mizolastine, terfenadine; ergot alkaloids: dihydroergotamine, ergometrine (ergonovine), ergotamine, methylergometrine (methylergonovine), eletriptan; irinotecan; lurasidone, oral midazolam, pimozide, sertindole, triazolam; bepridil, felodipine, lercanidipine, nisoldipine; ivabradine, ranolazine; eplerenone; cisapride; lovastatin, simvastatin, atorvastatin; colchicine in patients with impaired liver or kidney function.

Current or history of chronic heart failure (with the exception of therapy for life-threatening or other dangerous infections(see section "Special Instructions"). Fructose intolerance, sucrase-isomaltase deficiency, glucose-galactose malabsorption. Pregnancy and lactation.

FROM caution: with cirrhosis of the liver; severe violations liver and kidney function; hypersensitivity to other azoles; in elderly patients; in children (see also section "Precautions").

Overdose

Symptoms: overdose is accompanied by an increase in side effects.

Symptomatic treatment: gastric lavage with sodium bicarbonate solution, activated charcoal.

Itraconazole is not excreted by dialysis, there is no specific antidote.

Precautionary measures

Cross hypersensitivity reactions

Itraconazole should be used with caution in patients with hypersensitivity to other azoles.

Influence on cardiac activity

Itraconazole has a negative inotropic effect. There have been reports of cases of chronic heart failure associated with taking the drug. At a daily dose of 400 mg of itraconazole, a more frequent occurrence of heart failure was observed; at lower daily doses, this pattern was not revealed. The risk of chronic heart failure appears to be proportional to the daily dose. Itraconazole should not be taken in patients with or with a history of chronic heart failure unless the potential benefit far outweighs the potential risk. In an individual assessment of the benefit-risk ratio, the following factors are taken into account: the severity of the indication, the dosing regimen and individual risk factors for heart failure ( ischemic disease heart disease, valvular disease, obstructive pulmonary disease, renal failure, and other diseases accompanied by edema). Patients should be informed about the signs and symptoms of chronic heart failure and monitored for their occurrence during the course of treatment. If such signs appear, the drug should be discontinued.

Calcium channel blockers may have a negative inotropic effect, which may enhance the similar effect of itraconazole. Itraconazole may also reduce the metabolism of calcium channel blockers. Caution should be exercised when taking itraconazole and calcium channel blockers due to an increased risk of congestive heart failure.

Simultaneous administration of itraconazole and a number of CYP3A4 inhibitors (cisapride, pimozide, quinidine, levomethadone, etc.) is contraindicated due to identified cases of life-threatening arrhythmias and/or sudden death.

Effect on liver function

In very rare cases, severe toxic liver damage has developed with the use of itraconazole, including several cases of acute liver failure with a fatal outcome. In most cases, this occurred in patients who already had liver disease, in patients with other serious diseases in whom the drug was prescribed for the treatment of systemic diseases, as well as in patients receiving other drugs that have a hepatotoxic effect. However, some patients had no comorbidities or obvious risk factors for liver damage. Several of these cases occurred in the first month of therapy, and some in the first week of therapy. In this regard, it is recommended to regularly monitor liver function in patients receiving itraconazole therapy. In the event of symptoms suggesting the onset of hepatitis, namely: anorexia, nausea, vomiting, weakness, abdominal pain and dark urine, it is necessary to immediately stop treatment and conduct a study of liver function. The appointment of itraconazole in patients with an increase in the activity of "liver" enzymes or liver disease in the active phase, or in case of toxic liver damage due to the use of other drugs, should be carried out after assessing the risk-benefit ratio. In the case of the appointment of a drug, during treatment it is necessary to control the activity of "liver" enzymes. Itraconazole is predominantly metabolized in the liver. Since the total elimination half-life of itraconazole is slightly increased in patients with impaired liver function, it is recommended to monitor plasma concentrations of itraconazole and, if necessary, adjust the dose of the drug.

Decreased acidity of the stomach

With reduced acidity of gastric juice, the absorption of itraconazole from capsules is impaired. Patients taking antacid drugs (for example, aluminum hydroxide) are advised to take them no earlier than 2 hours after taking Itraconazole capsules. Patients taking medicines that reduce the acidity of gastric juice (blockers of Hg-histamine receptors or inhibitors proton pump), it is recommended to take itraconazole with acidic drinks to normalize absorption. The antifungal activity of the drug should be monitored and the dose increased if necessary.

Use in elderly patients

The use of the drug Itraconazole in the elderly is possible if the potential benefit of treatment outweighs the possible risk.

Kidney dysfunction

Data on the use of itraconazole in patients with impaired renal function are limited, in some patients with impaired renal function, itraconazole exposure may be reduced. In such patients, the drug Itraconazole is prescribed with caution. It is recommended to monitor the concentration of itraconazole in plasma and, if necessary, adjust the dose of the drug.

hearing loss

Transient or permanent hearing loss has been reported in patients taking itraconazole. In some cases, hearing loss occurred against the background of simultaneous administration with quinidine. Hearing usually recovers after the end of drug therapy, however, in some patients, hearing loss is irreversible.

Patients with immunodeficiency

In some immunocompromised patients, such as neutropenic patients diagnosed with AIDS or after organ transplantation, the oral bioavailability of itraconazole may be reduced. The attending physician should evaluate the need for maintenance therapy in AIDS patients who have previously received treatment for systemic fungal infections, such as sporotrichosis, blastomycosis, histoplasmosis, or cryptococcosis (both meningeal and non-meningeal), who are at risk of relapse.

Patients with life-threatening systemic fungal infections

Fluconazole-resistant strainsCandida are insensitive to itraconazole. neuropathy

If peripheral neuropathy occurs, which may be associated with itraconazole, treatment should be discontinued.

Disorders of carbohydrate metabolism

Contains sucrose. Taking the drug Itraconazole is contraindicated in patients with rare hereditary diseases: congenital galactosemia, lactase deficiency, glucose / galactose malabsorption syndrome or sucrase-isomaltase deficiency.

Cross hypersensitivity

There are no data on the presence of cross-hypersensitivity between itraconazole and other antifungal agents with an azole structure (from the azole group). In the presence of hypersensitivity to other azoles, itraconazole should be administered with caution.

Application in pediatric practice

Since clinical data on the use of itraconazole in children are insufficient, it is recommended to prescribe itraconazole to children if the possible benefit of treatment outweighs the potential risk.

Use by women of childbearing age

Women of childbearing potential taking Itraconazole should use adequate contraceptive methods throughout the course of treatment, up to the onset of the first menstruation after its completion.

Use during pregnancy and lactation

Pregnancy

Itraconazole should not be used during pregnancy except in the treatment of life-threatening infections when the expected benefit to the woman outweighs the potential risk to the fetus.

Women of childbearing age during the period of taking the drug Itraconazole must use adequate methods of contraception throughout the course of treatment, until the onset of the first menstruation after its completion.

Period breastfeeding

Since itraconazole can penetrate into breast milk, if necessary, use during breastfeeding should stop breastfeeding.

Influence on the ability to drive vehicles and control mechanisms

If you need to drive vehicles and work with mechanisms during the use of the drug Itraconazole, you should consider the possibility of adverse reactions, such as dizziness, visual impairment and hearing loss (see section "Side effects"). If the described adverse events occur, you should refrain from performing these activities.

Interaction with other drugs

It is important to inform prescribers of a new drug that you are taking Itraconazole.

Medicines that provide influence of itraconazole metabolism

Itraconazole is mainly metabolized with the participation of the CYP3A4 isoenzyme.

When itraconazole interacts with powerful isoenzyme inducersCYP3 A4 (rifampicin, rifabutin and phenytoin) the bioavailability of itraconazole and hydroxyitraconazole is significantly reduced, which leads to a significant decrease in the effectiveness of the drug and, accordingly, simultaneous use with these drugs is not recommended. A similar effect can be expected when itraconazole interacts with other inducers of microsomal liver enzymes (carbamazepine, phenobarbital and isoniazid).

Powerful isoenzyme inhibitorsCYP3 A4 (ritonavir, indinavir, clarithromycin and erythromycin) may increase the bioavailability of itraconazole.

The effect of itraconazole on metabolism zm other medicines

Enzymatically metabolized drugsCYP3 A4

Itraconazole may inhibit the metabolism of drugs metabolized by the cytochrome CYP3A4 enzyme, resulting in an increase and/or prolongation of the duration of action of these drugs. therapeutic effect. Examples of drugs that may be elevated by itraconazole exposure are shown in Table 1. Drugs that interact with itraconazole are divided into the following categories:

"Contraindicated" - drugs, the simultaneous administration of which in combination with itraconazole and within two weeks after stopping itraconazole is contraindicated; "Not recommended" - it is recommended to avoid the use of these drugs during treatment and for two weeks after stopping itraconazole, unless the expected benefit outweighs the potential risk; "Use with caution" means medicinal products which, when co-administered in combination with itraconazole, require monitoring of plasma concentrations, clinical effects and possible adverse reactions.

Table 1

Medicines that reduce the acidity of gastric juice (antacids, H blockers)] - histamine prescriptionsmoat, proton pump blockers)

Content

For the treatment of acute and chronic candidiasis caused by yeast or other fungi, Itraconazole is intended - the instructions for use of the drug contain information about correct use and dosage regimen. The drug is aimed at the destruction of fungal infections of the nails and skin, helps with infection by various strains of microorganisms. Check out his instructions.

Capsules Itraconazole

The accepted pharmacological classification classifies Itraconazole as antifungal drugs broad action. The drug contains the active ingredient itraconazole in micropellets. Due to its constituent components, the drug stops the production of vital substances for the fungal pathogen, which leads to cell death.

Composition of Itraconazole

The active substance of the drug is itraconazole at a concentration of 100 mg per capsule. Hard gelatin capsules of opaque pink color with a blue cap contain white-cream spherical microgranules inside. Check out the detailed composition of the drug:

Pharmacodynamics and pharmacokinetics

Synthetic antifungal agent works on many pathogens. The active substance is a derivative of triazole, inhibits the production of ergosterol in the fungal cell membrane. The drug destroys dermatophytes, yeast, mold fungi. The effectiveness of treatment can be assessed one month after the start of treatment with mycotic diseases of the skin, after 6-9 months with damage to the nails.

Itraconazole is absorbed in the stomach and intestines, with food intake increases its bioavailability. When using the solution on an empty stomach, the rate of reaching the maximum concentration becomes higher. Capsules begin to act four hours after ingestion, the active substance binds to plasma proteins by 99%. The drug penetrates into tissues, organs, the mucous membrane of the vagina, the secret of the sebaceous and sweat glands.

The clinical concentration of the agent in the skin is reached a week after the first day of treatment with Itraconazole and lasts for 30 days after the completion of a monthly course, in the keratin of the nails - a week after and remains for six months after the completion of a three-month course. Metabolism of Itraconazole occurs in the liver, metabolites are inhibitors of isoenzymes. The agent is excreted from the plasma by the kidneys within a week and by the intestines in two days, and is not removed during dialysis.

Indications for use

According to the instructions, indications for the use of the drug are the following conditions:

• vulvovaginal candidiasis;
• dermatomycosis;
• multi-colored lichen;
• candidiasis of the oral mucosa;
• keratomycosis, onychomycosis (nail fungus);
• systemic mycoses of the skin - aspergillosis, candidiasis, cryptococcosis, cryptococcal meningitis;
• histoplasmosis, blastomycosis, sporotrichosis, paracoccidioidomycosis.

Method of application and dosage

Itraconazole tablets for oral administration are administered orally after meals, they are swallowed whole, washed down clean water. The dosage indicated in the instructions depends on the clinical picture:

special instructions

The instructions for Itraconazole contain an item special instructions, which should be examined by each patient before use:

• Patients of childbearing age should be reliably protected by contraceptives until the first menstruation after the end of the course.
• The drug has a negative inotropic effect, which can lead to chronic heart failure.
• With a reduced acidity of the stomach, the absorption of the contents of the capsules slows down.
• Very rarely, when using capsules, the development of severe toxic liver damage is possible.
• The bioavailability of Itraconazole is reduced in patients with impaired immunity, with AIDS, after organ transplantation.
• The drug is not prescribed for children, only if the expected benefit exceeds the possible risk.
• Itraconazole can cause dizziness, which adversely affects the control of mechanisms.

drug interaction

The instruction says the following drug interactions Itraconazole when used with other medicines:

• Antacids should be taken two hours after taking Itraconazole, with achlorhydria or in combination with histamine receptor blockers, the capsules are washed down with cola.
• Rifampicin, Rifabutin, Phenytoin reduce the effectiveness of the drug.
• Ritonavir, Indinavir, Clarithromycin increase the bioavailability of the substance.
• The agent is incompatible with Terfenadine, Mizolastin, Lovastatin, Triazolam, ergot alkaloids, slow calcium channel blockers.
• Anticancer drugs, immunosuppressive agents, glucocorticosteroids require a dosage reduction when combined with itraconazole.

Side effects

In case of overdose, gastric lavage is indicated, activated carbon. When using the drug, according to the instructions and reviews, side effects may occur:

• nausea, vomiting, constipation, abdominal pain, appetite disorders;
• hepatitis, acute liver failure;
• headaches, dizziness, neuropathy;
• anaphylactic and allergic reactions;
• erythema of the skin, rash, photosensitivity;
• menstrual disorders, hypokalemia, pulmonary edema.

Contraindications

The instructions for the drug say about some features of the reception and contraindications, in which the use of the drug is prohibited:

• hypersensitivity to components;
• chronic heart failure;
• pregnancy, breastfeeding;
• children's and adolescence up to 18 years;
• under medical supervision, the drug is taken for renal and hepatic insufficiency, peripheral neuropathy, hearing loss, in old age.

Structural formula

Russian name

Latin name of the substance Itraconazole

chemical name

4-methoxy]phenyl]-1-piperazinyl]phenyl]-2,4-dihydro-2-(1-methylpropyl)-3H-1,2,4-triazol-3-one

Gross formula

Pharmacological group of the substance Itraconazole

Nosological classification (ICD-10)

CAS code

Characteristics of the substance Itraconazole

An antifungal agent from the group of triazole derivatives. White or slightly yellowish powder. Insoluble in water, very slightly soluble in alcohols, freely soluble in dichloromethane. Lipophilene, partition coefficient (octanol / water at pH 8.1) - 5.66. Molecular weight - 705.64.

Pharmacology

Research in vitro demonstrated that itraconazole inhibits cytochrome P450-dependent synthesis of ergosterol, an essential component of the fungal cell membrane.

Active against dermatophytes (Trichophyton spp., Microsporum spp., Epidermophyton floccosum), yeast-like fungi Candida spp.(including C.albicans, C.glabrata, C.krusei), fungi (Cryptococcus neoformans, Aspergillus spp., Histoplasma spp., Paracoccidioides brasiliensis, Sporothrix schenckii, Fonsecaea spp., Cladosporium spp., Blastomyces dermatitidis) and etc.

The bioavailability of itraconazole ranges from 40-100%, depending on dosage form and acceptance conditions.

The pharmacokinetics of itraconazole following intravenous administration and its absolute oral bioavailability as a solution were studied in a randomized crossover study in 6 healthy male volunteers; the observed bioavailability when taking the solution inside was 55%. Bioavailability was higher when the solution was taken on an empty stomach: in 27 healthy male volunteers, AUC values ​​0-24 h at steady state when taken on an empty stomach were 131 ± 30% of those observed when taken after a meal.

The bioavailability of itraconazole capsules is maximal when the capsules are taken immediately after a heavy meal. In a crossover study in 6 healthy male volunteers who received itraconazole 100 mg capsules immediately after a hearty meal or without it, C max was 132 ± 67 ng / ml and 38 ± 20 ng / ml, respectively. Absorption of itraconazole on an empty stomach is variable and depends on the level of intragastric acidity (relative or absolute achlorhydria). There was a decrease in bioavailability in patients with AIDS, as well as in volunteers who received suppressors of gastric secretion (for example, H 2 - antihistamines) and increased absorption - when taking itraconazole capsules simultaneously with cola. In a crossover study in 18 AIDS patients, it was shown that when taking 200 mg of itraconazole on an empty stomach simultaneously with cola (compared to taking the same amount of water), AUC 0-24 values ​​increased by 75 ± 121%, C max increased by 95 ± 128 %.

C max is reached after 3-4 hours, the equilibrium concentration in plasma (when administered 100-200 mg 1-2 times a day) - within 15 days and is (3-4 hours after taking the last dose): 0.4 mcg / ml (when taking 100 mg 1 time per day), 1.1 μg / ml or 2 μg / ml (200 mg 1 or 2 times a day). Plasma protein binding - 99.8% (itraconazole), 99.5% (hydroxyitraconazole). Penetrates into tissues and organs (including the vagina), is contained in the secretion of the sebaceous and sweat glands. Accumulates in the lungs, kidneys, liver, bones, stomach, spleen, skeletal muscles (the concentration of itraconazole in these tissues exceeds plasma levels by 2-3 times. Concentrations in keratin-containing tissues, especially in the skin, are 4 times higher than plasma levels. Itraconazole is found in nail keratin already 1 week after the start of treatment and persists for at least 6 months after a 3-month course of treatment, in the skin - for 2-4 weeks after a 4-week intake Poorly passes through the BBB Biotransformed in the liver (mainly with the participation CYP3A4) with the formation of a large number of metabolites, including active (hydroxyitraconazole) Excreted by the kidneys (less than 0.03% unchanged, about 40% as inactive metabolites) and with faeces (3-18% unchanged In patients with renal insufficiency, bioavailability is slightly reduced compared to patients with normal renal function.In patients with cirrhosis of the liver, T 1/2 is increased.

Decreased cardiac contractility

With the on / in the introduction of itraconazole to anesthetized dogs, a dose-dependent negative inotropic effect was observed. In a study in healthy volunteers, i.v. injections of itraconazole resulted in a transient, asymptomatic decrease in left ventricular ejection fraction (until the next infusion - after 12 hours - these changes disappeared).

The use of the substance Itraconazole

Mycoses of the skin, mucous membranes of the oral cavity and eyes; onychomycosis caused by dermatophytes, yeast and mold fungi; candidiasis with damage to the skin and mucous membranes, incl. vulvovaginal candidiasis; pityriasis versicolor; systemic mycoses, incl. aspergillosis (with resistance or poor tolerance to amphotericin B), cryptococcosis (including cryptococcal meningitis), histoplasmosis, sporotrichosis, paracoccidioidomycosis, blastomycosis.

Contraindications

Hypersensitivity.

Application restrictions

Chronic heart failure, incl. in history (use is possible only in cases where the expected benefit outweighs the potential risk), cirrhosis of the liver, renal failure, childhood(safety and efficacy in children have not been determined).

Use during pregnancy and lactation

Use during pregnancy is allowed only for systemic mycoses in cases where the expected effect outweighs the potential risk to the fetus.

Nursing mothers should stop breastfeeding (itraconazole passes into breast milk).

Side effects of Itraconazole

From the digestive tract: dyspepsia, nausea, abdominal pain, anorexia, vomiting, constipation, increased activity of liver transaminases, hepatitis, in very rare cases - severe toxic liver damage, incl. case of acute liver failure with a fatal outcome.

From the nervous system and sensory organs: headache, dizziness, peripheral neuropathy, fatigue, drowsiness.

From the side of cardio-vascular system and blood (hematopoiesis, hemostasis): arterial hypertension. There have been reports of cases of chronic heart failure associated with the use of itraconazole.

From the genitourinary system: dysmenorrhea, edematous syndrome, albuminuria, urine staining in a dark color.

Allergic reactions: pruritus, rash, urticaria, angioedema, Stevens-Johnson syndrome.

Others: alopecia, hypokalemia, pulmonary edema, decreased libido, impotence.

Interaction

Incompatible with terfenadine, astemizole, cisapride, lovastatin, oral forms midazolam and triazolam. Enhances and / or prolongs the action of oral anticoagulants (including warfarin), cyclosporine, digoxin, methylprednisolone, vincristine, calcium channel blockers. Rifampicin and phenytoin reduce the bioavailability of itraconazole, inhibitors of cytochrome CYP3A4 (ritonavir, indinavir, clarithromycin) increase its bioavailability. Antacids reduce the absorption of itraconazole (the interval separating their intake should be at least 2 hours).

Overdose

Symptoms: increased adverse reactions.

Treatment: gastric lavage, activated charcoal, symptomatic therapy. Not removed during hemodialysis. There is no specific antidote.

Routes of administration

inside.

Itraconazole Substance Precautions

In immunocompromised patients (AIDS, organ transplant status, neutropenia), an increase in dose may be required (due to a decrease in the bioavailability of itraconazole).

When prescribing to patients with chronic heart failure, an individual assessment of the benefit-risk ratio is necessary, taking into account such factors as the severity of the indications, the dosing regimen, individual risk factors (presence of heart disease, including coronary artery disease, valvular disease), chronic obstructive pulmonary disease, renal failure. If signs or symptoms of congestive heart failure or neuropathy occur, treatment with itraconazole should be discontinued.

During treatment with itraconazole, it is necessary to monitor liver function (especially with long-term use). At elevated level transaminases are prescribed if the expected effect of therapy outweighs the possible risk of liver damage. In patients with cirrhosis of the liver and / or with impaired renal function, plasma concentrations of itraconazole should be monitored and the dose adjusted if necessary.

Women of childbearing age should use adequate methods of contraception throughout the course of treatment, up to the onset of the first menstruation after its completion.

Interactions with other active substances

Trade names