Voriconazole

When ATH:
J02AC03

Characteristic.

Antifungal system application from the group of triazoles.

White or light-colored powder. Molecular weight 349,31.

Pharmacological action.
Antifungal.

Application.

Invasive aspergillosis; severe forms of invasive Candida infections (including Сandida krusei), resistant to fluconazole; esophageal candidiasis, caused Сandida albicans, immunocompromised patients; severe fungal infections, caused Scedosporium spp. and Fusarium spp.; severe fungal infections intolerant or refractory to other drugs; prevention of "breakthrough" of fungal infections in febrile patients with high-risk groups (incl. after bone marrow transplantation, against the backdrop of relapse of leukemia).

Contraindications.

Hypersensitivity, simultaneous use with CYP3A4 substrates — terfenadine, astemizolom, cizapridom, pimozidom, xinidinom, sirolimusom, ergot alkaloids (ergotamin, digidroergotamin), simultaneous application of inducers of CYP450-rifampicin, carbamazepine and long-acting barbiturates (such as phenobarbital), ritonavirom (400 mg every 12 no), EFV (cm. "Interaction").

Restrictions apply.

Hypersensitivity to other azoles, severe liver failure, severe renal insufficiency (when administered parenterally), Age to 2 years (Safety and efficacy have not been established).

Pregnancy and breast-feeding.

Animal studies have shown, that voriconazole in high doses has toxic effects on the reproductive function. Voriconazole showed teratogenic effects in rats (cleft palate, gidronefroz / gidroureter), starting dose 10 mg / kg (0,3 recommended maintenance dose based on mg / m²), and embryotoxic effects in rabbits at doses 100 mg / kg (in 6 RAP times higher in terms of mg / m²). Other effects included in rats: reduction in the ossification of the sacral and caudal vertebrae, Skull, the pubic and the hyoid bone, additional ribs, anomaly segments of the sternum, dilatation of the ureter / renal pelvis. At all dose levels of plasma estradiol in pregnant rats was reduced. The use of voriconazole in rats led to an increase in the duration of pregnancy and difficult childbirth, It was associated with increased perinatal pup mortality at a dose 10 mg / kg. In rabbits, there was an increase embrioletalnosti, decreased fetal weights, and increased incidence of skeletal changes, cervical ribs and vnegrudinnyh places ossification.

In the case of voriconazole during pregnancy or if pregnancy occurs during treatment with voriconazole patient must be advised of the potential risk to the fetus.

Category actions result in FDA - D. (There is evidence of the risk of adverse effects of drugs on the human fetus, obtained in research or practice, However, the potential benefits, associated with drugs in pregnant, may justify its use, in spite of the possible risk, if the drug is needed in life-threatening situations or severe disease, when safer agents should not be used or are ineffective.)

Voriconazole should not be used in women, breast-feeding, except, the expected benefit outweighs the potential risk (excretion in breast milk has not been studied).

Side effects.

The most common adverse reactions, marked in clinical trials, We had visual impairment, fever, rash, vomiting, nausea, diarrhea, headache, sepsis, peripheral edema, abdominal pain, respiratory disorders. Improving indicators of liver tests, rash and visual impairment — side effects, associated with treatment, that most often led to discontinuation of therapy with voriconazole.

Side effects, observed when using voriconazole and, perhaps, They have been associated with the treatment of (n=1493):

From the nervous system and sensory organs: headache (3,2%), hallucinations (2,5%), dizziness (1,3%), blurred vision (20,6%), photophobia (2,4%), change of color (1,3%), bleeding in the retina (0,2%).

Cardio-vascular system and blood (hematopoiesis, hemostasis): tachycardia (2,5%), increased blood pressure (1,9%), decrease in blood pressure (1,7%, vasodilation (1,5%), thrombocytopenia (0,5%), anemia (0,1%), leukopenia (0,3%), pancytopenia (0,1%).

From the digestive tract: nausea (5,9%), vomiting (4,8%), abnormalities of liver function tests (2,7%), increase in liver function tests (1,9%), incl. increase in AP (3,6%), IS (1,9%), GOLD (1,8%), bilirubin (0,8%); abdominal pain (1,7%), diarrhea (1,1%), cholestatic jaundice (1,1%), dry mouth (1,0%), jaundice (0,2%).

With the genitourinary system: peripheral edema (1,1%), impairment of renal function (0,5%), acute renal failure (0,5%), creatinine increase (0,3%).

Allergic reactions: rash (5,8%), maculo-papular rash (1,1%), itch (1,1%).

Other: fever (6,2%), chills (4,1%), kaliopenia (1,6%), gipomagniemiya (1,1%), chest pain (0,9%).

Visual disturbances. When voriconazole treatment of frequent visual impairment. Approximately 30% patients experiencing a violation of visual perception: blurred vision, changes in color vision or photophobia. Visual disturbances are transient and fully reversible, in most cases they disappear spontaneously within 60 m. Repeated use of voriconazole marked weakening of their severity. Visual disturbances are usually easily expressed, rarely require discontinuation of treatment and do not lead to any consequences in the long term. Visual impairment may be associated with higher plasma concentrations and / or dosages of the drug.

The mechanism of their development is not known, though, likely, PM acts on the retina. In studying the effect of voriconazole on retinal function in healthy volunteers showed a reduction in the amplitude of the waves on the electroretinogram (Rpm). Changes in the ERG does not increase with continued treatment for 29 days and completely disappeared after the abolition of voriconazole. The effect of a long-term therapy with voriconazole (more 29 days) on visual function is not known.

Skin reactions. Often mentioned in the application of voriconazole skin reactions, but it should be noted, these patients had serious underlying medical conditions while taking other medicines. In most cases lesions were slightly or moderately expressed. In rare cases, treatment with voriconazole develop severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis and erythema multiforme.

When the rash the patient should be carefully monitored, and the progression of skin changes voriconazole advisable to cancel. Patients, receiving long-term therapy with voriconazole, may develop photosensitivity skin reactions (cm. Precautions).

Less common side effects, vstrechavshyesya in <1% All patients, poluchavshih voriconazole, including healthy volunteers (total n = 2090):

From the nervous system and sensory organs: asthenia, confusion, depression, alarm, tremor, ažitaciâ, paresthesia, ataxia, cephaledema, giperesteziya, Guillain Barre syndrome, extrapyramidal syndrome, nistagmo, reduction or enhancement of visual perception, mist, .Aloe, optic neuritis, papilledema, scleritis, diplopia, oculomotor disturbances, aglia, optic atrophy, violation of taste perception.

Cardio-vascular system and blood (hematopoiesis, hemostasis): atrial or ventricular arrhythmia, bradycardia, supraventricular tachycardia, OF блокада, ʙigeminija, QT prolongation, ventricular fibrillation, kardiomegalija, cardiomyopathy, hemorrhagic / ischemic stroke, heart failure, endokardit, arrythmia, cardiac arrest, myocardial infarction, tromboflebit, phlebitis, anemia (incl. macro-, normo- or microcytic, megaloblastnaya, aplastic), lymphadenopathy, agranulocytosis, DIC, limfangit.

From the respiratory system: respiratory distress syndrome, pulmonary edema, sinusitis.

From the digestive tract: peritonitis, increased levels of gamma-glutamyl transferase (GGT), LDH, bilirubin, cheilitis, cholelithiasis, cholecystitis, constipation, duodenitis, enlargement of the liver, gingivitis, glossitis, hepatitis, hepatic failure, pancreatitis, swelling of the tongue, psevdomembranoznыy colitis, pechenochnaya coma.

With the genitourinary system: hematuria, increase in BUN, albuminuria, jade, renal tubular necrosis.

For the skin: photosensitivity, alopecia, exfoliative dermatitis, purpura, toxic epidermal necrolysis (Lyell's syndrome), eczema, psoriasis, malignant exudative erythema (Stevens-Johnson syndrome), hives, angioedema, discoid lupus erythematosus, erythema multiforme.

Allergic reactions: edema, swelling of the face, anaphylactoid reactions (incl. flushing, Sweating, tachycardia, breathlessness, insensibility, nausea, itching and skin rash).

Other: ascites, cellulitis, flu-like symptoms, hyperthermia, pain syndrome (incl. backache, pain in the side, pelvic pain, chest pain), arthritis, reaction "graft versus host", Granules, infection, incl. bacterial and fungal infections, diseases of the mucous membranes, sepsis, insufficiency of the adrenal cortex, Hyper- or hypothyroidism, gipoglikemiâ, hypercholesterolemia, eozinofilija. Local reaction is pain, infection / inflammation at the injection site.

Liver function tests. The overall incidence of clinically significant increase of transaminases in patients, poluchavshih voriconazole, - 13,4%. Liver dysfunction may be associated with higher plasma concentrations and / or dosages of the drug. In most cases, liver function abnormalities disappear with continued treatment (without changing the dose, or after the correction) or termination. In the application of voriconazole rarely seen cases of severe hepatotoxicity in patients with serious underlying medical conditions. These cases may include cases of jaundice, hepatitis and hepatocellular insufficiency, leading to death.

Reaction, associated with infusion. The on/in infusion may experience vorikonazola anaphylactoidnye reaction, including tides blood to a person, fever, Sweating, taxikardiju, narrowing in Gruda, shortness of breath, insensibility, nausea, itching and rashes. These symptoms appear immediately after the start of infusions (cm. Precautions).

Cooperation.

Voriconazole is metabolized by the action of cytochrome p 450 CYP2C19 Isoenzymes, CYP2C9 и CYP3A4. Inhibitors or inducers of these isoenzymes may cause increase or decrease respectively, concentrations in plasma vorikonazola.

Vorikonazola levels in plasma are drastically reduced, while the application with the following HP:

Rifampicin (inducer of CYP450) -rifampicin (600 mg 1 once a day) reduces with_max plasma and AUC_τ vorikonazola on 93 and 96% respectively. The simultaneous use of vorikonazola and rifampicin is contraindicated (cm. "Contra").

Ritonavir (inducer of CYP450, the inhibitor and substrate of CYP3A4) -ritonavir (400 mg every 12 no) reduces with_max in equilibrium and AUC_τ vorikonazola, ingestable, on average 66 and 82% respectively. The effect of lower doses of ritonavir on the concentration of vorikonazola is not yet known. Established, that re-employment vorikonazola inside has no pronounced effect on with_max in equilibrium and AUC_τ Ritonavir, also received again. The simultaneous use of vorikonazola and ritonavir (400 mg every 12 no) contraindicated (cm. "Contra").

Carbamazepine and long-acting barbiturates, incl. phenobarbital (powerful inducers of CYP450) is probably, significantly reduce concentration in plasma vorikonazola, Although their interaction was not investigated. The simultaneous use of vorikonazola with carbamazepine and long-acting barbiturates is contraindicated (cm. "Contra").

Efavirenz (non-nucleoside reverse transcriptase inhibitor, inducer of CYP450, the inhibitor and substrate of CYP3A4) — equilibrium jefavirenz (400 mg 1 times a day inside) reduces equilibrium with_max и AUC_τ on average, vorikonazola 61 and 77% respectively. Voriconazole in equilibrium (400 mg inside every 12 h on the first day, then 200 mg inside every 12 h for 8 days) increases the equilibrium with_max и AUC_τ on average, jefavirenza 38 and 44% respectively. The simultaneous use of vorikonazola and jefavirenza counter (cm. "Contra").

Voriconazole inhibits the activity of isoenzymes of cytochrome p 450 CYP2C19, CYP2C9 и CYP3A4. In this regard, voriconazole may increase plasma concentrations of substances, which are metabolized by these izofermentami CYP450.

Contraindicated simultaneous application vorikonazola with the following HP:

Terfenadin, astemizol, cisapride, pimozide and quinidine (CYP3A4 substrates) — While the interaction with these drugs was not investigated, However, the simultaneous use of vorikonazola with terfenadine, astemizolom, cizapridom, pimozidom or hinidine contraindicated, tk. increasing concentrations of plasma may lead to longer QT interval and in rare cases to develop flicker/atrial fibrillation (cm. "Contra").

Sirolimus (a CYP3A4 substrate) -voriconazole improves with_max и AUC_τ sirolimusa (2 mg dose) on 556 and 1014% respectively. The simultaneous use of vorikonazola and sirolimusa counter (cm. "Contra").

Ergot alkaloids (CYP3A4 substrates) — While the interaction with these drugs was not investigated, Nevertheless, voriconazole may cause increased concentrations of alkaloids lpv (ergotamine and dihydroergotamine) in the plasma and the development of ergotism. The simultaneous use of alkaloids lpv with vorikonazolom counter (cm. "Contra").

Interaction with vorikonazolom can lead to higher blood concentrations of drugs, listed below. In this regard, when they are applying requires continuous monitoring and/or correction doses.

Cyclosporine (a CYP3A4 substrate) -in patients, undergoing a kidney transplant and are in stable condition, voriconazole improves with_max и AUC_τ Cyclosporine for at least 13 and 70% respectively. In the appointment vorikonazola patients, receiving cyclosporine, It is recommended to reduce the dose of Cyclosporine by half and control levels in plasma. Increasing the concentration of Cyclosporine Nephrotoxicity is accompanied by. After the abolition of vorikonazola need to monitor levels of Cyclosporine and, if necessary, increase the dose.

Tacrolimus (a CYP3A4 substrate) -voriconazole improves with_max и AUC_τ tacrolimus (0,1 mg / kg once) on 117 and 221% respectively. In the appointment vorikonazola patients, Receiving Tacrolimus, It is recommended to reduce the dose of the latter to 1/3 and control its levels in plasma. Increased levels of Tacrolimus is accompanied by Nephrotoxicity. After the abolition of vorikonazola need to monitor levels of Tacrolimus and, if necessary, increase the dose.

Warfarin (субстрат CYP2C9) -simultaneous application vorikonazola (300 mg 2 once a day) warfarin (30 mg dose) accompanied by an increase in the maximum PV to 93%. Together with the appointment of warfarin and vorikonazola to monitor the MF.

Other oral anticoagulants, for example patients, acenocoumarol (CYP2C9 substrates, CYP3A4) -voriconazole may cause increased concentrations of coumarins in plasma and PV. If sick, receiving the coumarin drugs, appoint voriconazole, There is a need to control PV with short intervals and appropriately select doses of anticoagulants.

Derived sulfonylureas (CYP2C9 substrates) -voriconazole may increase the concentration of derivatives sulfonylureas (for example tolbutamida, glipizide and gliburida) plasma and cause hypoglycemia. While their application, it is necessary to carefully monitor blood glucose levels.

Statynы (CYP3A4 substrates) - in vitro voriconazole inhibits metabolism lovastatina (in human liver Ca2). In this regard, may cause increased voriconazole plasma concentrations of Statins, metaboliziruthan under the influence of CYP3A4. When they are applying is recommended to assess the feasibility of dose adjustment of Statins. Raising the level of Statins sometimes accompanied by the development of rhabdomyolysis.

Benzodiazepines (CYP3A4 substrates) - in vitro voriconazole inhibits the metabolism of Midazolam (in human liver Ca2). In this regard, may cause increased voriconazole plasma levels of benzodiazepines, under the influence of which are metabolized by CYP3A4 (midazolam, triazolam, alprazolam), and development of prolonged sedation. In case of simultaneous use of these drugs is recommended to discuss the appropriateness of benzodiazepine dose adjustment.

Vinca alkaloids (CYP3A4 substrates) -can increase the content of voriconazole vinca alkaloids in plasma (for example vincristin and vinblastine) and cause neurotoxicity. It is recommended that you discuss the usefulness of dose adjustment vinca alkaloids.

Phenytoin (CYP2C9 substrate and a potent inducer of CYP450) — avoid the simultaneous application vorikonazola and fenitoina except, when the expected benefits outweigh the potential risks. Phenytoin (300 mg 1 once a day) reduces with_max и AUC_τ vorikonazola on 49 and 69% respectively. Voriconazole (400 mg 2 once a day) increases with_max и AUC_τ phenytoin (300 mg 1 once a day) on 67 and 81% respectively. Together with vorikonazolom we recommend that you carefully fenitoina monitored levels of fenitoina plasma. Phenytoin can be used together with vorikonazolom, If last dose was increased to 5 mg / kg every 12 h/b or c 200 to 400 mg every 12 h inside (with 100 to 200 mg every 12 h inside in patients weighing less than 40 kg).

Rifabutin (inducer of CYP450) -rifabutin (300 mg 1 once a day) reduces with_max и AUC_τ vorikonazola (200 mg 2 once a day) on 69 and 78% respectively. While appointing rifabutin with_max и AUC_τ vorikonazola dose 350 mg 2 times a day make up 96 and 68% from when you apply only vorikonazola the dose 200 mg 2 once a day. In applying vorikonazola in dose 400 mg 2 times per day_max и AUC_τ respectively 104 and 87% higher, than with monotherapy dose vorikonazolom 200 mg 2 once a day. Voriconazole in dose 400 mg 2 times a day increases with_max и AUC_τ of rifabutin 195 and 331% respectively. If the expected benefit from the treatment outweighs the risk of, rifabutin can be used in conjunction with vorikonazolom. In this case, the dose should be increased up to vorikonazola 5 mg / kg every 12 h/b or c 200 to 350 mg every 12 h inside (with 100 to 200 mg every 12 h inside in patients weighing less than 40 kg). While treatment rifabutinom and vorikonazolom it is recommended to regularly complete blood count and control the undesirable effects of rifabutin (for example, uveitis).

Omeprazole (CYP2C19 inhibitor; substrate CYP2C19 and CYP3A4) -omeprazole (40 mg 1 once a day) increases with_max и AUC_τ vorikonazola on 15 and 41% respectively. Vorikonazola dose adjustment is not recommended. Voriconazole improves with_max и AUC_τ omeprazole on 116 and 280% respectively. In the appointment vorikonazola patients, receiving omeprazole, the last recommended dose reduced by half. Voriconazole may also inhibit the metabolism of other Proton pump Blocker, who are CYP2C19 substrates.

Non-nucleoside reverse transcriptase inhibitors (CYP3A4 substrates, inhibitors or inducers of CYP450) — Research in vitro show, that delaverdin can inhibit the metabolism of vorikonazola; nevirapine can induce the metabolism of vorikonazola, Although this effect has not been studied; voriconazole may inhibit the metabolism of nonnucleoside reverse transcriptase inhibitors. If you are applying to vorikonazola with reverse transcriptase inhibitors non patients should be observed in order to identify possible toxic effects.

Given the small pharmacokinetic interaction or lack of meaningful interaction, does not require correction doses following HP:

Cimetidine (nonspecific inhibitor of CYP450, and increases the pH of gastric juice) -cimetidine (400 mg 2 once a day) increases with_max и AUC_τ vorikonazola on 18 and 23% respectively.

Ranitidine (raises the pH of gastric juice) -ranitidine (150 mg 2 once a day) does not have a significant effect at p_max и AUC_τ vorikonazola.

Macrolides-erythromycin (CYP3A4 inhibitor, 1 g 2 once a day) and azithromycin (500 mg 1 once a day) do not have a significant impact on with_max и AUC_τ vorikonazola.

Prednisolone (a CYP3A4 substrate) -voriconazole improves with_max и AUC_τ prednisolone (60 mg dose) on 11 and 34% respectively.

Digoxin (transport, mediated p-glycoproteins) -voriconazole has no significant effect on with_max и AUC_τ digoksina (0,25 mg 1 once a day).

Mycophenolic acid (substrate UDF-gljukuroniltransferazy) -voriconazole has no effect on with_max и AUC_τ mikofenolovoj acid (1 g once).

Indinavir sulfate (the inhibitor and substrate of CYP3A4) — indinavir sulfate (800 mg 3 once a day) have no significant impact on with_max и AUC_τ vorikonazola. Voriconazole does not significantly affect the C_max, C_min и AUC_τ indinavir sulfate (800 mg 3 once a day).

Other HIV protease inhibitors (substrates and inhibitors of CYP3A4) — Research in vitro indicates, that voriconazole may inhibit the metabolism of HIV protease inhibitors (such as saquinavir, nelfinavir and amprenavir), and that HIV protease inhibitors may inhibit the metabolism of vorikonazola. In the case of simultaneous use of vorikonazola with protease inhibitors for HIV patients should be observed in order to identify possible toxic effects.

Pharmaceutical incompatibility. Infuziu should not be vorikonazola through a catheter or cannula with other HP, including drugs for parenteral nutrition. However, it is possible the introduction of vorikonazola amid full parenteral nutrition via a separate entrance multi-channel catheter. Is not compatible with the solution of sodium bicarbonate 4,2% for / in infusion, compatibility with the solution in other concentrations are not known. Simultaneously with the introduction of vorikonazola there should be no blood products infusion.

Overdose.

When conducting clinical trials was observed three episodes of accidental overdose (children, who got in/in the dose, five times above the recommended). There was one case of fotofobia duration 10 m.

Treatment: simptomaticheskaya therapy. Antidote vorikonazola unknown. Voriconazole is removed when the ground with hemodialysis 121 ml / min. SBECD dializiruetsja with klirence 55 ml / min. In case of overdose Hepatology can promote the transfer of vorikonazola and SBECD from the body.

Dosing and Administration.

B /, inside. Inside, for 1 hours before or after 1 hours after meals. B /, infusion, at no more than 3 mg/kg/h for 1-2 h (not to introduce Jet). Before the in/in infuziei vorikonazola powder should dissolve and then further diluted.

Treatment (or oral) start with saturating doses (first 24 no), on the first day to achieve serum concentrations, close to equilibrium. Given the high bioavailability when administered (96%, cm. "Pharmacokinetics"), If there is clinical evidence can proceed with the oral medication.

Doses depend on evidence and body mass index patient. B /, saturating dose (all indications) - 6 mg / kg every 12 no, maintenance dose (After the first 24 no) -3-4 mg/kg every 12 no (depending on the evidence).

Inside, adults and children over 12 years, weighing at least 40 kg: saturating dose 400 mg every 12 no, supporting — 200 mg every 12 no; birth weight less than 40 kg: loading dose - 200 mg every 12 no, supporting — 100 mg every 12 no. Experience of the children from 2 to 12 years limited, that complicates selection of optimal dosages.

The duration of treatment depends on the clinical effect of mikologicheskogo and results analysis.

Dose adjustment is not required in older people.

Violation of the kidney does not affect the farmakokinetiku vorikonazola ingestion. In connection with this vorikonazola dose adjustment for intake in patients with light or expressed impaired kidney function not required. The on/in the introduction patients with moderate or expressed impaired kidney function (Cl creatinine <50 ml / min) There is a cumulation of the support component of the drug-SBECD. So sick voriconazole should appoint inwards, except, When the ratio of risks and benefits justifies it in/with the introduction of. In such situations there is a need to regularly monitor the levels of creatinine; in the case of its increase should discuss the possibility of moving to accept vorikonazola inside.

In acute liver damage, as reflected by the increased activity of liver transaminaz "" (GOLD, ACT), dose adjustment is not required. In such cases it is recommended to continue the monitoring of the performance of the functions of the liver, with a view to identifying further enhance.

In patients with mild or moderate hepatic insufficiency (Child-Pugh a and b) We recommend that you assign a standard shock dose, a dose decrease in 2 times. Patients expressed impaired liver voriconazole should be appointed only in cases, when the expected benefits outweigh the potential risks, and under constant review with a view to detect signs of toxicity.

Precautions.

Before therapy, adjust the electrolyte disorders such, as hypokalemia, hypomagnesemia and hypocalcemia.

Sampling for cultural and other laboratory studies (serology, histopathology) in order to highlight and identify pathogens should be performed before treatment. Therapy can be initiated, pending the outcome of the cultural and other laboratory studies, But if any treatment should be adjusted accordingly. Highlighted clinical strains, possessing a reduced sensitivity to vorikonazolu. However, elevated concentrations of suppressing minimum (IGC) It is not always possible to predict clinical inefficiency; There are cases, When voriconazole was effective in patients, infected with microorganisms, resistant to other azolam. To assess the correlation between activity in vitro and clinical results of the treatment of difficult, given the complexity of patients, which included in clinical research; the value of the border vorikonazola concentrations, to assess the sensitivity to this drug, not set.

Application of vorikonazola associated with undesirable phenomena on the part of the cardiovascular system: elongation QT interval on the ECG, accompanied by rare cases of atrial fibrillation flicker/patients, receiving vorikonazolom therapy (from seriously ill patients with multiple risk factors, such as kardiotoksicheskaja chemotherapy, cardiomyopathy, gipokaliemia and concomitant therapy, that could contribute to the development of this complication). Patients with data potentially proaritmičeskimi conditions voriconazole should be prescribed with caution.

Gepatotoksichnostь: When treating vorikonazolom there are infrequent (0,1–1%) cases of serious liver reactions (including reflected clinically hepatitis, cholestasis and hepatic cell failure, incl. fatal). Unwanted effects from the liver is mostly observed in patients with serious diseases (mostly malignant tumours of blood). In patients with no risk factors observed transient response from the liver, including hepatitis and jaundice. The liver is usually reversible and disappear after discontinuation of treatment. During treatment vorikonazolom it is recommended that you regularly monitor liver function, particularly liver function tests and bilirubin. With the appearance of clinical signs of liver disease, that may be associated with vorikonazolom, to discuss feasibility of cessation of therapy.

Patients have, receiving voriconazole, observed cases of acute renal failure. Such patients, probably, receive other nefrotoksicskie drugs and have concomitant diseases, the result of which could be reduced kidney function. During therapy requires grid kidney (laboratory research, incl. determination of serum creatinine).

When in/with the introduction of infusion reactions have been observed vorikonazola, mostly tides blood to a person and nausea. If these symptoms are expressed, You should discuss the advisability of stopping treatment.

In rare cases when treating vorikonazolom patients develop jeksfoliativnye skin reactions, such as Stevens-Johnson Syndrome. With the appearance of rash patients should watch, and with the progression of skin lesions voriconazole advisable cancel. Besides, application of vorikonazola accompanied by cutaneous photosensitivity reactions, especially when long-term therapy. During treatment, patients are advised to avoid intense or prolonged exposure to direct sunlight.

Women of reproductive age at the time of treatment must constantly use effective contraceptive methods.

Voriconazole may cause transient and reversible visual impairment, incl. mist, violation/enhancement of visual perception and/or photophobia. With these symptoms, patients should avoid performing potentially hazardous activities as, eg, driving a car or using complex technology. When taking vorikonazola patients should not drive a car at night.