Phycomycetes and other except Enomophthorales. Ketoconazole inhibits the biosynthesis of ergosterol in fungi, which leads to a change in composition of the lipid components of the dianabol cycle membranes. In the therapeutic dose of 200 mg a day, there may be a transient decrease in plasma testosterone concentrations.
The concentration of testosterone returned to baseline levels within 24 hours after administration of ketoconazole. During long-term treatment with this dose of testosterone concentration is usually slightly different from the control. Ketoconazole at a daily dose of 400 mg or more did not cause decrease in cortisol “response” to ACTH stimulation in volunteers. The maximum concentration of ketoconazole in the plasma of 3.5 mg / ml is achieved 1-2 hours after a single oral dose of 200 mg with food. after absorption from the gastrointestinal tract ketoconazole metabolized in the liver to a large number of inactive metabolites. The major metabolic pathways are oxidation and cleavage of imidazole and piperazine rings, oxidative and O-dealkylation aromatic hydroxylation. Ketoconazole is not an inducer of its own metabolism. About 13% of the dose excreted through the kidneys, of which from 2 to 4% of an unmodified drug substance. The preparation to stand out mainly with bile into the gastrointestinal tract. Elimination from the plasma is biphasic T1 / 2 = 2 hours for the first 10 hours and after 8 hours after. In vitro binding to plasma proteins, mainly albumin fraction is 99% . Only a small portion of the drug penetrates into the cerebrospinal fluid. Ketoconazole is a weak dibasic substance needing acidic medium for dissolution and absorption. The pharmacokinetic characteristics of ketoconazole in general differ slightly from healthy persons and patients with renal or hepatic insufficiency.
Infections smooth skin, the scalp, caused by dermatophytes and / or yeast fungi in cases where local treatment is not applicable due to the large size of the affected areas, a considerable depth of defeat, as well as the absence of effect of local treatment carried out previously:
- pityriasis versicolor
- folliculitis caused by fungi of the genus of Pityrosporum,
- esophageal candidiasis
- candidiasis of the mouth and pharynx,
- chronic skin and mucosal candidiasis,
- chronic recurrent vaginal candidiasis in the absence of the effect of local therapy.
Systemic fungal infections
Prophylactic dianabol cycle use in patients with a decrease in the body’s defenses (congenital or caused by disease or the influence of drugs), since in these cases increases the risk of fungal infections.
The use of ketoconazole in fungal meningitis is not advisable, since the drug does not penetrate the BBB.Contraindications
- Hypersensitivity to ketoconazole or excipients;
- children under 3 years (for a given dosage form) and weighing up to 15 kg (effectiveness and safety have been studied).
- acute or chronic liver disease;
- concomitant use with ketoconazole:
– substrates of CYP3A4: astemizole, terfenadine, bepridil, halofantrine, disopyramide, cisapride, dofetilide, levacetylmethadol, mizolastine, pimozide, quinidine, sertindole or because increasing the concentration of these drugs in the plasma may lead to a lengthening of the QT interval on the electrocardiogram and the development of ventricular arrhythmias by type «of torsade de pointe»;
– domperidone because possible lengthening of the interval QT;
– triazolam, and midazolam for oral use;
– HMG-CoA reductase metabolised CYP3A4, such as simvastatin and lovastatin;
– ergot alkaloids, such as dihydroergotamine, ergometrine, ergotamine, metilergometrina (metilergonovina)
– nisoldipine ;
(., see also “Interactions with other medicinal products” section);
- hereditary galactose intolerance, Lapp lactase deficiency or malabsorption of glucose-galactose.Precautions : concomitant use of drugs that reduce gastric acidity (antacids, H2 blockers, histamine receptors, proton pump inhibitors); women older than dianabol cycle 50 years, history of liver disease, drug intolerance, taking hepatotoxic drugs, duration of treatment with Oronazol more than 2 weeks; adrenal insufficiency function or patients undergoing major stress factors (extensive surgery, resuscitation, etc.); porphyria.Pregnancy and lactation
Currently there is limited information on the use of ketoconazole in pregnancy. In animal studies, reproductive toxicity of ketoconazole was discovered. The extent of the potential risk for humans is unknown.Thus tablets Oronazol should not be given to pregnant women except in cases where the potential benefit outweighs the potential risk for the fetus. Because ketoconazole passes into breast milk, breast-feeding is not recommended while taking Oronazola.
Dosage and administration
. Inside, during the meal to improve absorption of therapeutic use: Adults: One tablet (200 mg) once daily with a meal. If you are receiving the indicated doses of improvement does not occur, the dose should be doubled (400 mg once daily). Vaginal candidiasis: two tablets (400 mg) once daily with a meal. Children older than 3 years, ex: weighing 15 to 30 kg: 2.1 tablets (100 mg) once a day with a body weight of 30 kg doses indicated for adults.
- The average duration of treatment: vaginal candidiasis – 7 days ; cutaneous mycoses caused by dermatophytes – about 4 weeks, pityriasis versicolor – 10 days, the skin and oral candidiasis – 2-3 weeks; fungal scalp – 1-2 months, paracoccidioidomycosis, histoplasmosis, koktsidiodomikoz – usual duration of treatment is 6 months. for all indications, treatment should be carried out continuously until clinical parameters and laboratory parameters are not indicative of bacterial eradication.