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other ingredients: microcrystalline
cellulose (avicel PH 102), crosscarmellose sodium,
magnesium stearate, colloidal silicon dioxide,
butylated hydroxy toluole.
Pharmaceutical Form. Tablets.
Pharmacotherapeutic group.
Antifungal
agent for system use. Imidazole derivative.
Code ATC J02A B02.
Pharmacological properties.
Pharmacodynamics.
Ketoconazole – synthetical antifungal agent of
multiply action, effective for peroral use. It
slows down biosynthesis of ergosterol in fungal
and modifies the structure of other lipid
components of cell membrane. Makes fungicidal and
fungistatic action concerning dermatophytes
(Microsporum, Trichophyton,
Epidermophyton), yeasts (Candida,
Pityrosporum, Torulopsis, Cryptococcus),
dimorphous fungals (Histoplasma capsulatum,
Coccidioides, Paracoccidioidies)
eumycets and
other fungals. Such microorganisms as
Aspergillus spp., Sporothrix schenckii,
some types of Dermatiaceae, Mucor spp. and
others phykomycets, accept
Entomophthorales are less sensitive.
Ketoconazole is effective for treatment as local
as systemic fungal infections.
Ketoconazole depresses the action of some liver
enzymes P450, especially enzymes of group CYP3A,
and thus, it may reduce the excretion of medicine,
which are parallel prescribe, metabolism of which
depend on such enzymes. High doses (more than 400
mg/day) of ketoconazole reduse the reaction of
cortizol on ACTH stimulation. Prolong treatment
may reduce testosterone level in males.
Pharmacokinetics.
The absorption of all oral forms of
ketoconazole goes well: its bioavailability
reaches 75 % and serum concentration significantly
exceedes minimal inhibitory concentration
of most of fungal infections. The action of
ketoconazole is proportional to its dose. As it is
weak dibasic agent, it requires of acidic
medium for breakdown and absorption. Maximal
levels in plasma (in overage, nearly 3,5 mkg/ml)
are reach during 1-2 hours after peroral use of
single dose 200 mg of ketoconazole with food.
Ketoconazole is widely spread in organism; its
most highest concentration are determine in liver,
lungs, kidneys, (bone) marrow and myocardium. Only
insignificant quantity of ketoconazole gets in
cerebrospinal fluid. Ketocknazole approximately on
99 % connects with plasma protein (generally with
albumin) in vitro. Further excretion from plasma
is going on two stages with time of half life
of 2 hours during first 10 hours and time of
half life of 8 hours – in further. After
absorption from gastrointestinal tract the
ketoconazole transforms into several nonactive
metabolites. Nearly 13 % (of which 2-4 % - in
unchangeable form) of taking dose is excreted in
the urine. General way of excretion – in the
bile.
Indications.
-
subcutaneous or deep fungal infection of
skin, hair and nails, caused by dermatophytes
and/or yeasts (dermatomycosis, onychomycosis,
Candida perionyxis, pityriasis versicolor, dry
dandruff, folliculitis, caused by Pityrosporum,
chronic candidiasis, which affects skin and
mucous membrane), if these ifections can not be
treated by agents for external use or they don’t
reach to local therapy.
-
Candidiasis of oral cavity and
gastrointestinal tract.
-
Chronic and recurrent vaginal candidiasis.
-
System fungal infections (system
candidiasis, paracoccidioidomycosis,
histoplasmosis, coccidioidomycosis
blastomycosis).
-
Continuation of parenteral treatment by
myconazole.
-
Prophylactic treatment of patients with weak
immunity (which was inherited or caused by
disease or medicines), which have the risk of
injury by fungal infections.
As ketoconazole practically is not penetrate
from blood-brain barrier, DermazoleTM
don’t use for treatment of fungal meningitis.
Administration and Dosage:
For adults
For the treatment systemic infections of skin
and gastrointestinal tract for adults and children
with weight more than 30 kg it is recommended to
take 1 tablet of DermasoleTM (200 mg)
every day with food. If this dosage doesn’t call
an adequate reaction, the doctor may increase
dosage to 2 tablets (400 mg) per day. For children
with weight under 30 kg it is recommended
to take from 50 to 100 mg of ketoconazole per day
depending on body weight (about 3-5 mg/kg of body
weight per day).
In general, you should follow this diagram of
dosage not less negative mycology test. For the
treatment of vaginal candidiasis take 2 tablets
once a day during 5 days.
The average duration of treatment is the
following:
-
vaginal candidiasis – 5 days,
-
micosis, caused by dermatophytes – from 2 to
6 weeks,
-
pityriasis versicolor – 10 days,
-
micosis of oral cavity and skin, caused by
candides – from 2 to 3 weeks,
-
infections of hair – from 1 to 2 months,
-
infections of nails – from 6 to 12 months
(depend on the speed of nails growth, the
complete growth of injured nail is nesessary),
-
dermatomycosis – from 2 to 6 weeks,
-
systemic mycosis – from 1 to2 months,
-
coccidioidomycosis, paracoccidioidomycosis
or histoplasmosis – from 3 to 6 months.
For prophylaxis treatment of adults with
immunodeficiency it is recommended to take 2
tablets (400 mg) a day, and for children – 4-8
mg/kg of body weight, but no more than 400 mg a
day.
It is not need a special diminution of dosage
for patients, which suffer from kidney disease or
which are on dialysis.
Patients, who have acute and chronic liver
diseases can’t take the ketaconazole.
If you miss the dosage, you must take it
as soon as possible, because it must be constant
quantity of medicines in organism. If it is
less time for the next dosage according to
schedule, you should take only such next dosage,
without doubling.
Side effects.
Side effects of ketoconazole, as a rule, are
slight and have temporary character.
Sometimes unwanted gastrointestinal disorders,
such as dyspepsia, nausea, stomach-ache and
diarrhea may occur. Headache, reversible high
liver enzymes activity, menstrual cycle disorder,
dizziness, vomiting, photophobia, paresthesia, and
allergic reactions are rarely. In single cases
thrombocytopenia, alopecia, impotency and
reversible high intracranial pressure (edema and
inflammation of disk of optic nerve, protruded
little children’s crown) may be seen.
Also temporary diminution of testosterone level
in plasma may be seen, but it was brief, and
testosterone levels were within the limits of
normal meanings.
In usage higher dosage then prescribed,
sometimes gynecomastia and eligospermia may be
seen.
Very rarely idiosyncrasy hepatitis can be
developed, but it is reversible, if you repeat
this medicine immediately.
Contraindications.
Hypersensitivity to DermazoleTM or
other components of this product; acute and
chronic liver diseases.
Drug interactions.
Absorption of preparation is decreases if
falling of gastric acidity is depressed. Patients,
who take medicines, which decrease gastric acidity
(antacids, antagonists H2, proton pump
inhibitors) should take these drugs in two hours
after taking DermazoleTM.
Combination with isoniazid or inducers of liver
enzymes, such as rifampicin, reduces the level of
ketoconazole in blood. Such medicines mustn’t be
taken during the treatment by
DermazoleTM.
As ketokonazole depressed the action of some
P450 liver enzymes, especially CYP3A enzymes
group, it may reduce the removal of parallel
prescribing preparations, metabolism of which is
dependent on such enzymes. Increased levels of
such preparations can be connected with
intensifying and/or prolonging their therapeutic
action, including the possibility of side effects
risk.
Such examples of serious interactive are
known:
-
Terfenadine, astemizole, cisapride,
midozolam and triazolam in case of peroral use.
Increased level of terfenadine, astemizole or
cisapride can prolong interval QT in EKG.
Ventricular tachycardia of “ atrial
flutter-fibrillation” type is possible. Such
connecting can be observed with inhibitors of
GMG-CоА- reductase, such as
lovastatin. Such medicines are not to be taken
during treatment by ketoconazole. If midozolam
is prescribed intravenously, it is need special
prevented measures, because sedative effect of
this preparation can prolong.
-
Cyclosporine, anticoagulants,
methylprednisolone, bisulfane and
takrolimuce.
-
Dosages of these preparations should be
reduced. Alcohol response may be observed,
similar to disulfiram response (redness, skin
rash, peripheral hypostasis, nausea and
headache), these reactions completely lasts for
several hours.
Overdose.
Symptoms of overdose:
nausea, vomiting, dizziness and headache.
Sometimes it is enough to reduce dosage, and in
more difficult cases, which connecting with sense
of pricking and spasms, it should be discontinued
treatment by DermazoleTM. In case of
overdose you have to cause vomiting and irrigate
the gastric, and also take activated carbon. The
constant observation and symptomatic treatment are
necessary. There is no specific antidote for this
medicine.
Special indications.
DermazoleTM should be taken with
food for maximum absorption. Patients, who are
treating by ketoconazole, should know liver
disease symptoms, such as weakness and fever, dark
color of urine, pale color of faces, itch and
jaundiced. Patients must know about necessity of
discontinue treatment and should consult with
doctor. Factors, which increased the risk of
hepatitis: women over 50 years age, liver diseases
in anamnesis, known drug intolerance, prolonging
treatment with simultaneous usage of preparations,
which disturbed liver functions. It is recommended
to do blood test if the treatment lasts longer
then 2 weeks (before the treatment, in 2 weeks and
afterwards – every month). Insignificant temporary
increase of liver transaminases level or
alkaline phosphatase, which doesn’t convey with
symptoms, harmless and also doesn’t require
discontinue treatment. But such patients should be
observe. If level enzymes levels are increasing
more than 3 times by comparison with normal, the
therapy should be discontinue.
Ketoconazole reduces cortisol reaction for
stimulation of adrenocorticotropic hormone (ACTH).
Thus, it is necessary, to observe adrenal gland in
patients, who suffer from deficiency of its
function or when the adrenal gland function is
near with the normal, and also
patients, who during long period are in stress
conditions (big operations, intensive care
etc.).
Patients, who suffer from porphyria, must avoid
the treatment by ketoconazole.
Pregnancy and lactation
The studies of the preparation usage by
pregnant women were not carry out.
Thus ketokanazole should not be prescribed during
pregnancy, if only potential advantage for mother
is more than possible risk for fetus.
Ketoconazole exude into mother’s milk, thus you
should not breast-feed during the treatment.
Influence on ability to drive a car and
to operate any other machines.
In general, ketaconazole doesn’t
influence on ability to drive a car and to
operate any other machines, but some patients have
dizzy, caused by ketoconazole. Thus, patients, who
feel dizzy after taking this preparation, mustn’t
drive a car and other technical facilities.
Storage and Shelf-life. Keep out of
reach of children. Store in a dry and protected
from direct light place, at room temperature 15 -
25ºC. Shelf-life – 3 years.
Presentation. 10 tablets in a strip,
every in cardboard wrapper, 3 wrappers in a
cardboard box.
Name of Manufacturer.
Kusum Healthcare Pvt. Ltd.
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