The instruction for medical use
of DERMAZOL medicine
the Trade name
Mezhdunarodnoye the unlicensed
name Ketokonazol Lekarstvennaya a form
of the Tablet of 200 mg
One tablet contains
active agent – ketokonazol 200 mg,
excipients: microcrystalline cellulose, sodium of a kroskarmelloz, magnesium stearate, silicon dioxide colloidal, butyl hydroxytoluene.
of the Tablet of white color, round, with a biconvex surface.
Antifungal drugs for system use. Imidazole derivatives. Ketokonazol.
The ATX J02A B02 code
Pharmacokinetics At properties intake is well soaked up, especially in acidic environment of a stomach. The bioavailability is in direct dependence on the accepted dose. The maximum concentration (Cmax) is reached in 2 hours. In vitro linking with proteins of blood plasma, mainly with albumin fraction, makes 99%. Ketokonazol is widely distributed on fabrics, however only an insignificant part of drug gets into cerebrospinal fluid.
After absorption from digestive tract ketokonazol it is metabolized in a liver with formation of a large number of inactive metabolites. In the researches in vitro it was shown that CYP3A4 is the main enzyme which participates in metabolism of a ketokonazol. Highways of metabolism are oxidation and splitting of imidazolny and piperazinovy rings, oxidizing O-dealkylation and aromatic hydroxylation. Ketokonazol is not the inductor of own metabolism.
Removal from blood plasma is two-phase: within the first 10 hours the elimination half-life makes 2 hours, and in the next 8 hours.
About 13% of a dose are removed with urine of which from 2 to 4% are made by not changed medicinal substance. Drug is emitted generally with bile in digestive tract, at the same time about 57% of drug are removed with a stake.
Ketokonazol antifungal (fungicide) and fungistatic drug of a broad spectrum of activity. Slows down synthesis of ergosterol, the triglycerides and phospholipids necessary for synthesis of a cellular membrane of fungi (fungi lose colony-forming). It is active concerning the activator multi-colored depriving of Malassezia furfur, causative agents of some dermatomycoses (Trichophyton, Epidermophyton floccosum, Microsporum), causative agents of candidiasis (Candida) and also causative agents of system mycoses (Cryptococcus). It is active also concerning gram-positive cocci: Staphylococcus spp., Streptococcus spp.
For treatment of zhizneugrozhayushchy system (deep) mycoses:
the paracoccidioidosis, histoplasmosis, a coccidioidosis, a zymonematosis, chromomycosis
Because of risk of hepatotoxicity, the tablet Dermazol should be used only when the potential advantage outweighs potentially possible harm, also in view of existence of local dosage forms of a ketokonazol and other drugs.
The route of administration and doses
In system mycoses is appointed by the adult on 1 tablet once a day,
in case of lack of effect the dose can be increased to 2 tablets a
day within 10 days, the course of treatment can be continued more than 10 days
only after assessment of the response to therapy and control of a funution of a liver.
In case of the passed dose it is necessary to accept it as soon as possible
as in an organism it is necessary to maintain constant amount of medicine.
If before reception of the following dose according to the schedule there was a little
time, it is necessary to accept only the same following dose,
without doubling it.
are listed below the side effects noted with a frequency & ge, the patients with superficial and deep mycoses accepting ketokonazol have 1.0%:
– a headache
– nausea, an abdominal pain, diarrhea, an abnormal liver function.
The side effects noted with a frequency & le, 1.0%:
– a gynecomastia
– pains in an upper part of a stomach, vomiting, dyspepsia, a constipation, dryness in a mouth, a disgeziya, an abdominal distension, discoloration of language, hepatitis, jaundice
– anaphylactoid reactions
– dizziness, paresthesia, drowsiness, hyperexcitability, insomnia, alarm, fatigue, the general weakness
– intolerance of alcohol, anorexia, a lipidemia, increases in appetite, myalgia
– disturbance of a menstrual cycle
– nasal bleeding
– an alopecia, dermatitis, an erythema, a multiformny erythema, an itching, rash, allergic rash, a xeroderma, rushes of blood
– orthostatic pressure decline
– reduction of number of thrombocytes
– fever, peripheral hypostasis, a fever
– allergic reactions, including urticaria, an acute anaphylaxis, anaphylactic reactions, a Quincke’s disease
– adrenocortical insufficiency
– reversible increase in intracranial pressure
– heavy hepatotoxicity, including cholestatic hepatitis, gepatonekroz (biopsy), cirrhosis, a liver failure (including cases of transplantation and death)
– sharp generalized eczematic pustulez, photosensitivity
– an arthralgia
– erectile dysfunction, an azoospermism at the doses exceeding therapeutic-200 or 400 mg
of the Contraindication
– hypersensitivity to a ketokonazol or any of drug components
– acute or chronic diseases of a liver
– pregnancy and the period of a lactation
– children’s and teenage age up to 18 years
Contraindicated simultaneous use of the drug Dermazol with some substances which are CYP3A4 substrates. Increase in concentration of these medicinal substances in plasma as a result of their simultaneous use with ketokonazoly can lead to strengthening of therapeutic and undesirable action and also increase in its duration in such degree that it can serve as the cause of serious complications. For example, increase in concentration in plasma of some of these medicines can lead to increase in duration of an interval of QT and ventricular tachyarrhythmia, including ing of polymorphic ventricular tachycardia like pirouette – arrhythmias with a possible lethal outcome. Specific examples are given in the section Medicinal interactions.
Metabolism of a ketokonazol is carried out mainly with participation
of CYP3A4. Other substances which metabolism is carried out in the same way or which affect activity of CYP3A4 can influence pharmacokinetics of a ketokonazol. Similarly ketokonazol can change pharmacokinetics of other substances which metabolism is carried out the same way. Ketokonazol strong CYP3A4 inhibitor and R-glycoprotein. At simultaneous use of other drugs it is necessary to get acquainted with the corresponding iinstruktion on use for obtaining information on a way of metabolism and possible need of dose adjustment of drugs. Researches on studying interaction were conducted only at adults. The importance of the results received in these researches for use for children is unknown.
Medicines which can reduce concentration of a ketokonazol in plasma
Medicines which lower gastric acidity (for example, antiacid medicines, such as aluminum hydroxide, or substances suppressing acid secretion, for example, blockers of H2 of histamine receptors and inhibitors of a proton pomp) break absorption of a ketokonazol at its use in the form of tablets. At simultaneous use of these medicines with ketokonazoly in the form of tablets it is necessary to observe care:
– at simultaneous treatment by drugs which reduce acidity of gastric juice ketokonazol it is necessary to accept with acid drinks (such as not dietary Coca).
– antiacid medicines (for example, aluminum hydroxide) should be applied at least in 1 hour of di or in 2 hours after administration of drug Dermazol in tablets.
– at simultaneous use with other drugs it is necessary to control antifungal action, and if necessary the dose of a ketokonazol can be increased.
At simultaneous use of a keptokonazol with the strong inductors CYP3A4 possible such decrease in bioavailability of a ketokonazol which can lead to considerable decrease in its efficiency For example:
– antibacterial agents: an isoniazid, rifabutin, rifampicin
– anticonvulsant drugs: carbamazepine (see also subsection Medicines which concentration in plasma can increase), Phenytoinum
– antiviral means: efavirenz, not Virapinum.
In this regard use with ketokonazoly strong inductors of CYP3A4 enzyme is not recommended. It is necessary to abstain from use of these lekarstenny means in 2 weeks prior to and during treatment ketokonazoly, except for cases when the advantage exceeds risk of possible decrease in efficiency of a ketokonazol. At simultaneous use it is necessary to control antifungal action of a ketokonazol, and in need of its dose it is possible to increase.
Medicines which can increase concentration of a ketokonazol in plasma
Strong CYP3A4 inhibitors (for example, antiviral drugs, such as ritonavir, strengthened ritonaviry darunavir and strengthened ritonaviry fosamprenavir) can increase bioavailability of a ketokonazol. At simultaneous use of these medicines with ketokonazoly in a look tabletoksledut to be careful. For patients who have to accept ketokonazol along with strong CYP3A4 inhibitors it is necessary to carry out careful observation for identification of signs and symptoms of strengthening of pharmacological action of a ketokonazol or increase in its duration, and if necessary the dose of a ketokonazol should be lowered. If it is reasonable, it is necessary to define concentration of a ketokonazol in plasma.
Medicines which concentration in plasma can increase under the influence of a ketokonazol.
Ketokonazol can slow down metabolism of medicines which are metabolized by means of CYP3A4, and can suppress transport of medicines the R-glycoprotein. As a result of simultaneous use with ketokonazoly increase in concentration of these medicines and/or their active metabolites (a) in plasma is possible. Such increase in concentration in plasma can lead to strengthening of therapeutic and undesirable effect of these medicines or to increase in its duration. A possible contraindication is use of medicines which metabolism is carried out with the participation of CYP3A4 if it is known that they increase QT interval as such combination can lead to a ventricular tachyarrhythmia, including ing of polymorphic ventricular tachycardia like pirouette – arrhythmias with a possible lethal outcome. All medicines entering interaction can be divided into the following categories:
Are contraindicated: Medicine should not be applied along with ketokonazoly and also within one week after the treatment termination ketokonazoly under no circumstances.
It is not recommended: It is necessary to abstain from use of drug during treatment ketokonazoly or within one week after its termination, except for cases when the advantage exceeds possible increase in risk of emergence of side effects. If it is impossible to avoid simultaneous use of these drugs, it is recommended to control a clinical condition of the patient for determination of signs and symptoms of strengthening of action, increase in its duration or emergence of side effect of medicines in their interaction and also it is necessary to lower its dose or to temporarily stop administration of drug if it is considered necessary. If it is reasonable, it is necessary to define concentration of a ketokonazol in plasma.
To apply with care: At simultaneous use of medicine with ketokonazoly it is necessary to be careful. At simultaneous use for the patient the careful observation for determination of signs or symptoms of strengthening or increase in duration of action or emergence of side effects as a result of interaction of medicines has to be carried out and also it is necessary to lower its dose or to stop temporarily to the prima of drug if it is considered necessary. If it is reasonable, it is necessary to define concentration of a ketokonazol in plasma.
Examples of medicines which concentration in plasma can increase under the influence of a ketokonazol are provided on classes of medicines with the indication of recommendations of rather simultaneous use with ketokonazoly
instructions Hepatotoxicity before an initiation of treatment it is necessary to estimate function of a liver for an exception of acute or chronic diseases, during treatment it is necessary to monitorirovat often and regularly function of a liver at all patients to do not pass the first signs of hepatotoxicity. Against the background of reception of oral forms of a ketokonazol it was reported about very exceptional cases of emergence of heavy hepatotoxicity, including cases with a fatal outcome or the cases demanding liver transplantation. At some patients obvious risk factors concerning damage of a liver were not revealed. Several such cases arose in the first month of therapy, and treatments, some in the first week. Totally received Dermazol’s dose is risk factor of heavy hepatotoxicity. In this regard it is recommended to control each 2 weeks function of a liver at the patients receiving therapy ketokonazoly. Patsiyentov it is necessary to warn about need to contact immediately the doctor in case of the symptoms assuming developing of hepatitis, namely: anorexias, nausea, vomitings, weaknesses, jaundices, abdominal pain and darkenings of urine. In case of such symptoms it is necessary to stop immediately therapy and to conduct a research of function of a liver. Patients with increase in activity of liver enzymes or at the postponed toxic damage of a liver owing to intake of other drugs should not appoint the Dermazol drug treatment unless the expected advantage justifies risk of damage of a liver. In these cases it is necessary to control the level of liver enzymes during treatment.
Ketokonazol in a daily dose of 400 mg and caused decrease in the kortizolovy response to stimulation of AKTG in volunteers above. For this reason it is necessary to control function of adrenal glands at patients with adrenocortical insufficiency or borderline cases at the patients who are exposed to considerable stressful influences (extensive surgical interventions, conditions of intensive care, etc.), patients with a long course have therapies at suspicion on adrenocortical insufficiency.
The lowered acidity of a stomach
At the lowered acidity of a stomach absorption of a ketokonazol worsens. At persons with the lowered acidity of a stomach caused by diseases (for example, at persons with an achlorhydria) or at the same time used drugs (for example, at persons who accept the medicines lowering acidity of a stomach), it is recommended to use the drug Dermazol with acid drinks (such as not dietary Coca). It is necessary to control antifungal action of a ketokonazol and if necessary a dose of drug it is possible to increase.
Possible medicinal interactions
At simultaneous use of a ketokonazol with certain medicines the change of efficiency of a ketokonazol and/or at the same time used drug, emergence of life-threatening effects and/or a sudden lethal outcome is possible. Medicines which simultaneous use with ketokonazoly is contraindicated it is not recommended or which should be applied with care are listed in the section Medicinal interactions.
Features of influence of medicine on ability to run the vehicle or potentially dangerous mechanisms
Considering side effects of drug it is necessary to be careful when driving and other potentially dangerous mechanisms.
Symptoms – nausea, fatigue, including drowsiness and block, vomiting, an abdominal pain, anorexia, including loss of weight, loss of appetite, hyperaemia, including the increased sweating, hypostases, a gynecomastia, rash, including eczema, a purpura, dermatitis, diarrhea, a headache, a dysgeusia, an alopecia.
Treatment: Careful control of a condition of the patient and symptomatic treatment. Within the first hour after administration of drug it is possible to appoint activated carbon.
The form of release and packing
On 10 tablets place in planimetric bezjyacheykovy packing. On 1 planimetric bezjyacheykovy packing together with the instruction for medical use in the state and Russian languages in a cardboard pack.
On 3 cardboard packs place in a cardboard box.
To Store storage conditions in the dry, protected from light place at a temperature not over 25C.
To store out of children’s reach!
not to apply a period of storage after expiry date.
According to the prescription
the Producer Kusum Heltker Pvt.
Ltd., JV 289 (A), Riiko Indl. Area, Chopanki, Bkhivadi (Raj.), India
Owner of the registration certificate
Kusum Heltker Pvt. Ltd., India
the Address of the organization accepting in the territory of the Republic of Kazakhstan claims from consumers on quality of products (goods)
Representative office of Kusum Heltker Pvt Association. Ltd., India in RK
Almaty, Dostyk Ave 117/6
ph. / fax: 295-26-50, 295-26-55