Vfend - Instructions For Use, Price, Tablets, Suspension, Analogues

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Vfend

Vfend: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. Use in childhood
11. 11. In case of impaired renal function
12. 12. For violations of liver function
13. 13. Use in the elderly
14. 14. Drug interactions
15. 15. Analogs
16. 16. Terms and conditions of storage
17. 17. Terms of dispensing from pharmacies
18. 18. Reviews
19. 19. Price in pharmacies

Latin name: Vifend

ATX code: J02AC03

Active ingredient: voriconazole (voriconazole)

Producer: Pfizer Manufacturing Deutschland, GmbH (Germany)

Description and photo update: 2019-23-08

Prices in pharmacies: from 4950 rubles.

Buy

Vfend is a drug with an anti-fungal effect.

Release form and composition

Vfend dosage forms:

• film-coated tablets: almost white or white, biconvex, Pfizer engraved on one side; 50 mg each - round, engraved on the other side - "VOR50"; 200 mg - oblong shape, engraving on the other side - "VOR200" (2 pcs. in blisters, in a cardboard box 1 blister; 7 pcs. in blisters, in a cardboard box 1, 2, 4 or 8 blisters; 10 pcs. in blisters, in a cardboard box 1, 3, 5 or 10 blisters);
• powder for preparation of suspension for oral administration: powder and the resulting suspension of almost white or white color (in vials of 45 g / 100 ml, in a cardboard box 1 bottle complete with adapter, syringe and measuring cup);
• lyophilisate for preparation of solution for infusion: white powder; the reconstituted solution is colorless, transparent (in vials of 3.4 g, in a cardboard box 1 bottle).

Composition of 1 Vfend tablet:

• active substance: voriconazole - 50 or 200 mg;
• auxiliary components (50/200 mg): lactose monohydrate - 62.5 / 250 mg; pregelatinized starch - 21/84 mg; croscarmellose sodium - 7.5 / 30 mg; povidone - 7.5 / 30 mg; magnesium stearate - 1.5 / 6 mg;
• shell (50/200 mg): Opadry white OY-LS-28914 (hypromellose, titanium dioxide, lactose monohydrate, glycerol triacetate) - 3.75 / 15 mg.

Composition of 1 ml of ready-made Vfend suspension:

• active substance: voriconazole - 40 mg;
• auxiliary components: colloidal silicon dioxide - 1 mg; sucrose - 542.4 mg; titanium dioxide - 1 mg; sodium benzoate - 2.4 mg; xanthan gum - 2 mg; orange flavor - 4 mg; sodium citrate dihydrate - 3 mg; citric acid - 4.2 mg.

Composition of 1 bottle of Vfend lyophilisate:

• active substance: voriconazole - 200 mg;
• auxiliary component: betadex sodium sulfobutylate - 3200 mg.

Pharmacological properties

Pharmacodynamics

Voriconazole is a broad-spectrum antifungal drug that belongs to the triazole group. Its mechanism of action is to inhibit the fungal cytochrome P ₄₅₀, which is the most important step in the biosynthesis of ergosterol. The accumulation of 14α-methylsterol correlates with the further loss of ergosterol in the cell membranes of fungi, which is the manifestation of the antifungal activity of voriconazole. Studies have confirmed that Vfend's active ingredient demonstrates greater selectivity for cytochrome P ₄₅₀ isoenzymes characteristic of fungi than for various cytochrome P ₄₅₀ enzyme systems acting in mammals.

A positive relationship between the minimum, maximum and average values of the concentration of voriconazole in the blood plasma and the effectiveness of Vfend in the course of therapeutic studies was not found, and this relationship was not the subject of preventive studies.

Pharmacodynamic and pharmacokinetic analysis of the results of the above clinical studies proved the presence of a positive relationship between the content of the active component of Vfend in the blood plasma and deviations from the normal values of the biochemical parameters of the liver function, as well as violations of the organ of vision.

In vitro voriconazole is characterized by a broad spectrum of antifungal activity, showing activity against Candida spp. (including fairly resistant strains of Candida albicans and Candida glabrata, as well as Candida krusei strains resistant to fluconazole). Vfend demonstrates a fungicidal effect against all strains of Aspergillus spp., Which were the object of clinical studies, and pathogenic fungi that often infect the human body in recent years (including Fusarium spp. Or Scedosporium spp., Showing limited sensitivity to currently known antifungal drugs).

Voriconazole has been proven to be clinically effective (with partial or complete response) in infectious diseases caused by pathogens of the Aspergillus spp. (including A. nidulans, A. flavus, A. niger, A. terreus, A. fumigatus) and Candida spp. (including C. tropicalis, C. albicans, C. parapsilosis, C. krusei, C. glabrata), as well as in infections provoked by a limited number of strains of Candida guilliermondii, Candida inconspicua, Candida dubliniensis, Scedosporium spp. (including S. proliftcans and S. apiospenmun) and Fusarium spp.

Vfend was also used (with both partial and complete response) in some cases in patients with fungal infections provoked by Trichosporon spp. (including T. beigelii), Alternaria spp., Scopulariopsis brevicaulis, Blastomyces dermatitidis, Phialophora richardsiae, Cladosporium spp., Penicillium spp. (including P. marneffei), Coccidioides immitis, Paecilomyces lilacinus, Conidiobolus coronatus, Madurella mycetomatis, Cryptococcus neoformans, Fonsecaea pedrosoi, Exophiala spinifera, Exserohilum rostratum.

In vitro voriconazole shows activity against clinical strains Histoplasma capsulatum, Acremonium spp., Cladophialophora spp., Bipolaris spp., Alternaria spp. Suppression of multiplication of most strains was observed in the voriconazole concentration range of 0.05–2 μg / ml.

Voriconazole has also been found to act in vitro against Sporothrix spp. and Curvularia spp., however, the clinical significance of this effect is not well understood.

Pharmacokinetics

The pharmacokinetic parameters of voriconazole are characterized by significant interindividual variability. The pharmacokinetics of this substance is non-linear due to the saturation of its metabolism. Increasing the dose leads to a disproportionate (more pronounced) increase in the area under the concentration-time curve (AUC _T). An increase in the daily dose of Vfend when taken orally from 400 mg to 600 mg (divided into 2 doses) causes an increase in AUC _Tby about 2.5 times. With oral administration of voriconazole at a maintenance dose of 200 mg (or 100 mg in patients whose body weight does not exceed 40 kg), the effect of the drug corresponds to its effect when administered intravenously at a dose of 3 mg / kg. When taken orally, Vfend at a maintenance dose of 300 mg (or 150 mg in patients weighing less than 40 kg), the effect is similar to that of voriconazole when administered intravenously at a dose of 4 mg / kg.

With oral administration or intravenous administration of saturating doses of the drug, the equilibrium concentration of voriconazole is achieved within the first 24 hours. If Vfend is prescribed 2 times a day at medium (but not saturating) doses, voriconazole accumulates, and equilibrium concentrations are recorded in most patients by the 6th day after starting treatment.

Voriconazole is rapidly and almost 100% absorbed after oral administration, and its maximum concentration in blood plasma is determined 1-2 hours after administration. The oral bioavailability of the substance is 96%. When taken again with food containing large amounts of fat, the maximum concentration and AUC _T decrease by 34% and 24%, respectively, the pH of the gastric juice does not affect the absorption of voriconazole.

On average, the volume of distribution of the drug after reaching equilibrium is approximately 4.6 l / kg, which indicates an active distribution of voriconazole in the tissues. The degree of binding to blood plasma proteins reaches 58%. Voriconazole crosses the blood-brain barrier and is found in cerebrospinal fluid.

As evidenced by the results of in vitro studies, isoenzymes CYP3A4, CYP2C9, CYP2C19 are involved in the metabolism of voriconazole. One of the key roles in the metabolism of voriconazole is played by the isoenzyme CYP2C19, which has a pronounced genetic polymorphism. This causes a decrease in the metabolism of voriconazole, which occurs in 3-5% of representatives of the black and Caucasian races and in 15-20% of residents of Asian countries. It has been proven that in patients with reduced metabolism AUC _{T of the} active component of Vfend is approximately 4 times higher than in homozygous patients with a high degree of metabolism.

The main metabolite of voriconazole is considered to be N-oxide, the proportion of which reaches approximately 72% of the total amount of radioactively labeled metabolites circulating in blood plasma. This metabolite is characterized by insignificant antifungal activity, therefore its contribution to the therapeutic effect of voriconazole is minimal.

Voriconazole is excreted as metabolites resulting from biotransformation in the liver. Less than 2% of the dose of the drug entered the body is excreted unchanged in the urine.

After repeated oral administration or intravenous administration of voriconazole, approximately 83% and 80% of the dose of the drug, respectively, is determined in the urine. At the same time, both after oral administration and after intravenous administration, most of the total dose (more than 94%) is excreted during the first 96 hours. The half-life of the drug is determined by the size of the dose and is equal to approximately 6 hours with oral administration of Vfend at a dose of 200 mg. Since the pharmacokinetics of voriconazole is non-linear, it is not possible to predict the cumulation or excretion characteristics of the active substance from the half-life.

With repeated oral administration of the drug, the maximum concentration and AUC _T in healthy young women were 83% and 113% higher, respectively, than in healthy young male patients (age ranged from 18 to 45 years). Clinically significant differences in the maximum concentration and AUC _T in healthy women and men of advanced age (over 65 years) were not found. The equilibrium concentration of the active substance Vfend in blood plasma in female patients was 91% and 100% higher than in male patients after taking voriconazole in the form of a suspension or tablets, respectively. There is no need to adjust the dose of the drug depending on gender. The content of voriconazole in blood plasma in women and men is almost identical.

With repeated oral administration of Vfend tablets, the maximum concentration and AUC _T in healthy elderly men (65 years of age and older) were 61% and 86% higher than these indicators typical for healthy young men aged 18 to 45 years. Differences in the values of the maximum concentration and AUC _T in healthy young women (age from 18 to 45 years) and healthy women of advanced age (65 years and older) are not clinically significant.

The safety profile of voriconazole in elderly and young patients does not differ significantly. No dose adjustment of Vfend is required depending on the patient's age.

With voriconazole, there is greater intraindividual variability in children than in adults. When comparing the adult and child populations, it was found that the probable AUC _Tin children after administration of a saturating dose of 9 mg / kg, it was comparable with this indicator in adults after administration of a saturating dose of 6 mg / kg. After administration of a maintenance dose of 4 mg / kg and 8 mg / kg 2 times a day to children, the estimated total concentration also approached that in adults after administration of the drug at a maintenance dose of 3 mg / kg and 4 mg / kg 2 times a day. When voriconazole was administered intravenously at a dose of 8 mg / kg, its concentration was 2 times higher than that when the drug was taken orally at a dose of 9 mg / kg. When taken orally, the bioavailability of voriconazole in children can be limited by a rather low body weight and malabsorption at this age, therefore, in this case, intravenous administration of Vfend is sometimes preferable.

The results obtained confirm the higher elimination of the drug in children compared with adults, which is explained by the large ratio of liver weight to total body weight.

In adolescents, the content of voriconazole in blood plasma is predominantly similar to this indicator in adult patients. However, some adolescents with low body weight had lower plasma concentrations of the active substance Vfend compared to adults, which turned out to be closer to the values of this indicator in children. In accordance with the data of population pharmacokinetic analysis, adolescents aged 12-14 years, whose body weight does not exceed 50 kg, should receive voriconazole at the dose recommended for use in children.

With a single oral administration of Vfend at a dose of 200 mg in patients with normal renal function and in patients with renal dysfunctions ranging from mild (CC 41-60 ml / min) to severe (CC less than 20 ml / min) the pharmacokinetic parameters of voriconazole do not significantly change depending on the severity of renal dysfunction. In patients with varying degrees of renal failure, voriconazole binds to blood plasma proteins in almost the same way. The accumulation of betadex sodium sulfobutylate, an auxiliary substance that is part of the lyophilisate for preparing a solution for infusion, is observed in patients with severe or moderate renal dysfunction.

A single oral administration of Vfend at a dose of 200 mg in patients with mild to moderate liver cirrhosis (classes A and B according to the Child-Pugh scale) led to an increase in the AUC _{T of} voriconazole by 233% compared with patients with normal liver function. Liver dysfunctions do not affect the degree of binding of the active substance to blood plasma proteins. With repeated administration of voriconazole inside its AUC _Tcomparable in patients with normal liver function taking Vfend at a dosage of 200 mg 2 times a day, and in patients with moderate liver cirrhosis (class B according to the Child-Pugh scale) taking the drug in a maintenance daily dose of 200 mg, broken for 2 receptions. There is no information on the pharmacokinetics of voriconazole in patients with severe liver cirrhosis (class C according to the Child-Pugh scale).

Indications for use

• fungal infections in severe cases in cases of intolerance / refractoriness to other drugs;
• invasive aspergillosis;
• esophageal candidiasis;
• invasive forms of candidal infections in severe course (including Candida krusei);
• severe fungal infections caused by Scedosporium spp. and Fusarium spp.;
• "Breakthrough" fungal infections in high-risk patients (patients with recurrent leukemia, recipients of allogeneic bone marrow), with fever (for prophylactic purposes).

Contraindications

• combined use with CYP3A4 substrates (terfenadine, astemizole, cisapride, pimozide, quinidine), sirolimus, carbamazepine, rifampicin, long-acting barbiturates, ritonavir, ergot alkaloids, efavirenz;
• age up to 2 years (the safety profile for this group of patients has not been studied);
• individual intolerance to the components of the drug.

According to the instructions, Vfend should be used with caution in the presence of the following diseases / conditions:

• severe liver failure;
• renal failure in severe course (parenteral administration);
• pregnancy and the period of breastfeeding (the safety profile for this group of patients has not been studied; the use of Vfend is possible only in cases where the expected benefit exceeds the possible risk);
• hypersensitivity to other drugs - derivatives of azoles.

When using Vfend, women of reproductive age should use reliable methods of contraception.

Instructions for using Vfend: method and dosage

How to use Vfend:

• tablets, suspension: inside, the recommended interval with food intake is 1 hour;
• infusion solution: infusion at a rate of up to 3 mg / kg / h for 1–3 hours. Injection is not recommended.

Before starting therapy, the following electrolyte disturbances should be corrected: hypokalemia, hypocalcemia and hypomagnesemia.

Therapy in adult patients should be started with intravenous administration at the recommended saturating dose, this will allow reaching an adequate plasma concentration of the active substance in the blood already on the first day. Vfend is administered intravenously for at least 7 days, then the patient is transferred to oral administration of the drug without adjusting the dosage regimen.

The recommended single dose, which is used every 12 hours (intravenous infusion / oral administration with a weight of up to 40 kg / oral administration with a weight of more than 40 kg; a saturating dose is prescribed for all indications, a maintenance dose is used after the first 24 hours of therapy, it is determined by the indications; 100 mg corresponds to 2.5 ml of Vfend suspension):

• saturating dose: 6 mg per kg / not recommended / not recommended;
• invasive aspergillosis, infections caused by Scedosporium spp. and Fusarium spp., other severe invasive fungal infections: 4 mg per kg / 100 mg / 200 mg;
• invasive fungal infections in adults and children from 12 years of age, belonging to the high-risk group, "breakthrough" fungal infections in febrile patients (with a prophylactic purpose); candidemia without signs of neutropenia: 3-4 mg per kg / 100 mg / 200 mg;
• esophageal candidiasis: not established / 100 mg / 200 mg.

In cases of insufficient effectiveness of therapy, the maintenance single dose for oral administration can be increased: patients weighing up to 40 kg - from 100 to 150 mg, with a weight of more than 40 kg - from 200 to 300 mg.

If the increased dose is poorly tolerated, it is reduced in steps of 50 mg to the initial one.

The duration of the course should be as short as possible. It is determined by the clinical effect and the results of mycological studies. The maximum duration is 180 days.

Prophylactic use of Vfend in adults and children should be started on the day of transplantation. The duration of the course is up to 100 days. An increase in the duration of the drug use up to 180 days is possible only in cases of continued immunosuppressive treatment or with the development of a graft-versus-host reaction (GRT).

The effectiveness and safety of using Vfend for more than 180 days have not been studied.

The dosage regimen for prophylactic purposes is the same as for therapeutic purposes.

In acute disorders of hepatic function, which are manifested as an increase in the activity of hepatic transaminases (alanine aminotransferase and aspartate aminotransferase), dose adjustment should not be carried out, but it is recommended to monitor liver function indicators.

For mild / moderate impairment of hepatic function (classes A and B according to the Child-Pugh classification), the saturating dose is administered in a standard amount, the maintenance dose should be reduced by 2 times. In case of severe liver dysfunction (class C according to Child-Pugh classification), Vfend is prescribed only in cases where the expected benefit is higher than the possible harm, while constant monitoring of the indicators is necessary to identify signs of the toxic effect of the drug.

The experience of using Vfend in children is limited, which makes it difficult to determine the optimal scheme for its use.

For children 2–12 years old, the following single doses are recommended with a frequency of use every 12 hours (regardless of the method of administration):

• saturating dose (first 24 hours): 6 mg / kg;
• maintenance dose (after the first 24 hours of therapy): 4 mg / kg.

If a child can swallow tablets, the dose in mg / kg is rounded to the nearest multiple of 50 mg. The drug is prescribed as whole tablets. Tolerance and pharmacokinetics of higher doses in children have not been studied.

For children 12-16 years old, Vfend is prescribed in the same way as for adult patients.

To prepare the suspension, you need to open the bottle, add 46 ml of water (2 measuring cups of 23 ml each) and shake the drug vigorously for 1 minute. It is recommended to use a measuring syringe for correct dosage. The suspension bottle should be shaken before each use.

To prepare the infusion solution, the contents of the vial must be dissolved in water for injection with a volume of 19 ml. The resulting concentrate of 20 ml contains 10 mg / ml of voriconazole. If the solvent did not enter the bottle under the influence of vacuum, then Vfend cannot be used.

Before use, the concentrate is added in the required volume to the recommended compatible solution for infusion to obtain a solution with a concentration of 0.5–5 mg / ml.

Recommended solutions:

• 0.9% or 0.45% sodium chloride solution;
• complex solution of sodium lactate;
• 5% glucose solution;
• 5% glucose solution and 0.45% or 0.9% sodium chloride solution;
• 5% glucose solution and complex sodium lactate solution;
• 5% glucose solution in 20 meq potassium chloride solution.

Side effects

Most often, during the period of therapy, the development of such adverse reactions as headache, visual disturbances, rash, fever, vomiting, diarrhea, nausea, abdominal pain, peripheral edema is noted. As a rule, these violations are mild or moderate.

Possible side effects (> 10% - very common;> 1% and 0.1% and 0.01% and <0.1% - rarely; <0.01% - very rare):

• cardiovascular system: often - thrombophlebitis, lowering blood pressure, phlebitis; rarely - ventricular arrhythmia, atrial arrhythmias, tachycardia, bradycardia, prolongation of the QT interval, supraventricular tachycardia, ventricular fibrillation; very rarely - nodal arrhythmias, bundle branch block, complete AV block, ventricular tachycardia (including ventricular flutter);
• digestive system: very often - abdominal pain, diarrhea, nausea, vomiting; often - cholestatic jaundice, gastroenteritis, increased liver function indicators, cheilitis, jaundice; rarely - dyspepsia, cholecystitis, duodenitis, cholelithiasis, constipation, liver enlargement, peritonitis, gingivitis, liver failure, glossitis, hepatitis, tongue edema, pancreatitis; very rarely - hepatic coma, pseudomembranous colitis;
• lymphatic system and blood: often - thrombocytopenia, anemia (including macrocytic, microcytic, megaloblastic, normocytic, aplastic), pancytopenia, leukopenia; rarely - lymphadenopathy, eosinophilia, agranulocytosis, inhibition of bone marrow hematopoiesis, disseminated intravascular coagulation syndrome; very rarely - lymphangitis;
• immune system: rarely - anaphylactoid / allergic reactions;
• nervous system: very often - headache; often - hallucinations, dizziness, tremors, confusion, anxiety, depression, paresthesia, agitation; rarely - fainting, nystagmus, ataxia, cerebral edema, hypesthesia, hypertension; very rarely - Guillain-Barré syndrome, insomnia, drowsiness during infusion, encephalopathy, extrapyramidal syndrome, oculomotor crisis;
• respiratory system: often - sinusitis, pulmonary edema, respiratory distress syndrome;
• musculoskeletal system: often - back pain; rarely - arthritis;
• endocrine system: rarely - insufficiency of the adrenal cortex; very rarely - hypothyroidism, hyperthyroidism;
• genitourinary system: often - hematuria, acute renal failure, increased creatinine; rarely - albuminuria, increased residual urea nitrogen, nephritis; very rarely - necrosis of the kidney tubules;
• sense organs: very often - visual disturbances (including changes in color vision, fog in front of the eyes, disturbance / enhancement of visual perception, photophobia); rarely - diplopia, scleritis, blepharitis, optic neuritis, swelling of the optic nipple, impaired taste; very rarely - hypoacusia, optic nerve atrophy, retinal hemorrhage, corneal opacity, ringing in the ears;
• subcutaneous tissue and skin: very often - rash; often - maculopapular rash, pruritus, alopecia, purpura, skin photosensitivity reactions, facial edema, exfoliative dermatitis; rarely - urticaria, fixed drug rash, psoriasis, eczema, Stevens-Johnson syndrome; very rarely - toxic epidermal necrolysis, angioneurotic edema, erythema multiforme, discoid lupus erythematosus;
• metabolism and nutrition: often - hypoglycemia, hypokalemia; rarely - hypercholesterolemia;
• general: very often - peripheral edema, fever; often - asthenia, chills, inflammation / reactions at the injection site, chest pain, flu-like syndrome.

Overdose

At least three cases of unintentional overdose are known when using Vfend in the form of an infusion solution. All of them relate to pediatric patients to whom voriconazole was administered intravenously at a dose 5 times higher than the recommended dose.

A single case of photophobia lasting 10 minutes has also been reported. There is no specific antidote for voriconazole, therefore, with the introduction of high doses of the drug, supportive and symptomatic therapy is recommended.

The active substance of Vfend is excreted by hemodialysis, and the clearance is 121 ml / min. In the same way, betadex sodium sulfobutylate (SBECD) is eliminated with a clearance of 55 ml / min.

special instructions

During the period of therapy, infrequent cases of the development of serious liver disorders (including clinically manifested hepatitis, hepatic cell failure and cholestasis, including with a fatal outcome) were noted. As a rule, these side effects of Vfend are observed in patients with serious diseases (mainly malignant blood tumors). In the absence of any risk factors, transient liver reactions may develop, including jaundice and hepatitis. In most cases, hepatic impairment is reversible and transient.

During the use of Vfend, it is recommended to regularly monitor liver function, in particular the level of bilirubin and liver function tests. In cases of clinical signs of liver disease associated with voriconazole therapy, the feasibility of discontinuing treatment should be assessed.

In order to identify possible adverse events from the kidneys, laboratory studies should be carried out, in particular, the determination of serum creatinine levels is required.

If during the intravenous administration of Vfend, pronounced infusion reactions develop (mainly in the form of flushing and nausea), the expediency of further therapy should be assessed.

In rare cases, exfoliative skin reactions, such as Stevens-Johnson syndrome, are noted during therapy. When a rash develops, the patient's condition should be monitored; if the disorder progresses, Vfend is usually discontinued. It is also possible to develop skin photosensitivity reactions, especially during long-term treatment. During the treatment period, it is recommended to avoid prolonged / intense exposure to direct sunlight.

Influence on the ability to drive vehicles and complex mechanisms

Considering the profile of adverse reactions, including the likelihood of developing visual impairments (fog before the eyes, photophobia, increased / impaired visual perception), as well as dizziness, it is recommended to refuse to drive vehicles while taking Vfend, especially at night.

Application during pregnancy and lactation

There is no adequate data on the safety of using Vfend during gestation, therefore it is not recommended to use the drug during pregnancy. The doctor may decide to prescribe a drug to a pregnant woman, provided that the expected benefits of treatment exceed the possible risks to the health of the fetus.

Experimental studies carried out in animals have confirmed the toxic effects of high doses of voriconazole on reproductive function. The potential risk to human health is unknown.

The excretion of voriconazole in breast milk has not been studied, therefore, it is not recommended to prescribe the drug during lactation. An exception can be made when the expected benefits of breastfeeding outweigh the risks to the health of the child.

Women of reproductive age who are taking Vfend should use reliable contraceptive means.

Pediatric use

Children under the age of 2 years are not prescribed Vfend due to the lack of data on the safety and efficacy of the drug in this category of patients.

With impaired renal function

In patients with renal dysfunction, there is no need to adjust the dosage regimen for oral administration. When using Vfend in the form of a solution for infusion, it is necessary to take into account that in patients with moderate or severe renal impairment (CC less than 50 ml / min), accumulation of an auxiliary substance (SBECD) is observed. For this reason, this category of patients is recommended to prescribe the drug orally, except in cases where the expected benefit from intravenous administration significantly outweighs the potential risk. At the same time, regular monitoring of the creatinine level is necessary, and if it increases, the possibility of transferring the patient to voriconazole intake should be considered.

A 4-hour hemodialysis session does not lead to the elimination of a significant part of voriconazole and does not require a dose adjustment of Vfend.

For violations of liver function

For patients with severely impaired liver function, Vfend is prescribed with caution, provided that the expected benefits exceed the possible risks. The liver function should be monitored regularly during the entire period of treatment and, if signs of toxic effects of the drug appear, consider stopping therapy.

Use in the elderly

In elderly patients, there is no need for dose adjustment.

Drug interactions

Combined use of Vfend with certain drugs / substances may result in the following effects:

• rifampicin, ritonavir, carbamazepine and long-acting barbiturates: significant decrease in voriconazole plasma levels; the combination is contraindicated;
• terfenadine, cisapride, astemizole, pimozide, quinidine: an increase in their plasma concentration, which can lead to a prolongation of the QT interval and, in some cases, to ventricular fibrillation / flutter; the combination is contraindicated;
• sirolimus: an increase in its plasma concentration; the combination is contraindicated;
• ergot alkaloids: an increase in their plasma concentration, which can lead to the development of ergotism; the combination is contraindicated;
• sulfonylurea derivatives, statins, vinca alkaloids, benzodiazepines, cyclosporine, tacrolimus, warfarin, other oral anticoagulants, including phenprocoumon, acenocoumarol: an increase in their concentration in the blood, during the period of therapy, constant monitoring of the patient's condition is necessary and, possibly, dose adjustment;
• efavirenz: mutual influence on plasma concentration; the combination is contraindicated;
• phenytoin: mutual influence on plasma concentration; the combination is recommended to be avoided, except in cases where the expected benefit is higher than the possible risk; combined use requires an increase in the maintenance dose of Vfend from 200 to 400 mg and from 100 to 200 mg (patients weighing more than 40 kg / less than 40 kg), as well as careful monitoring of the plasma level of phenytoin;
• rifabutin: mutual influence on plasma concentration; the combination is recommended to be avoided, except in cases where the expected benefit is higher than the possible risk; combined use requires an increase in the maintenance dose of Vfend from 200 to 350 mg and from 100 to 200 mg (patients weighing more than 40 kg / less than 40 kg), as well as regular monitoring of a detailed blood test and unwanted effects of rifabutin (for example, uveitis);
• omeprazole: mutual influence on plasma concentration; it is recommended to reduce the dose of omeprazole by 2 times;
• other HIV protease inhibitors (eg saquinavir, amprenavir, nelfinavir): suppression of voriconazole metabolism; with combined use, observation is necessary to identify possible toxic effects;
• other non-nucleoside reverse transcriptase inhibitors: possible inhibition of voriconazole metabolism; with combined use, observation of the condition of patients is required to identify possible toxic effects.

Vfend should not be infused through the same cannula / catheter with other drugs, including drugs for parenteral nutrition. Voriconazole can be administered concurrently with complete parenteral nutrition through a separate port on a multichannel catheter.

4.2% sodium bicarbonate solution for intravenous infusion is incompatible with voriconazole, therefore it is not recommended to use it as a solvent.

Simultaneous administration of Vfend solution with infusions of blood preparations should be avoided.

Analogs

Vfend analogs are: Voriconazole-Teva, Voriconazole Canon, Voriconazole Sandoz, Voriconazole-Acri, Voricoz, Vikand, Biflurin, Diflucan, Mikosist, Fluconazole, etc.

Terms and conditions of storage

Keep out of the reach of children. Store at temperature:

• tablets, lyophilisate for the preparation of infusion solution - up to 30 ° C;
• powder for preparation of a suspension for oral administration - 2–8 ° С.

Shelf life:

• tablets, lyophilisate for the preparation of infusion solution - 3 years;
• powder for preparation of suspension for oral administration - 2 years.

The reconstituted infusion solution can be used for 24 hours at a storage temperature of 2 to 8 ° C.

The finished suspension can be taken for 14 days at a storage temperature of up to 30 ° C.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Vfend

According to reviews, Vfend has proven itself as a first-line drug used for the treatment of invasive aspergillosis diagnosed in patients undergoing immunosuppressive therapy for myeloma and granulomatous disease. It is also successfully used in patients with acute leukemia (for example, lymphoblastic leukemia), suffering from fungal infections of the lungs and other organs. Vfend is considered to be a good prophylactic agent preventing invasive mycoses during allogeneic organ transplantation. Its effectiveness and safety have been confirmed by numerous patient reviews. Voriconazole is reported to be more active against Aspergillus than itraconazole, has greater oral bioavailability and is less toxic.

Vfend also often helps patients with HIV, accompanied by esophageal candidiasis and refractory fungal infections, provided they have a long course of treatment (at least several months). However, many patients do not like the high cost of the drug.

Price for Vfend in pharmacies

The approximate price for Vfend in the form of tablets with a dosage of 200 mg is RUB 16,450–20,391 (per pack containing 14 pcs.). You can buy a powder for preparing a suspension for oral administration for approximately 10,600-16,500 rubles, and a lyophilisate for preparing a solution for infusion - for 3175-6189 rubles.

Vfend: prices in online pharmacies

Drug name Price Pharmacy

Vfend 200 mg lyophilisate for preparation of solution for infusion 1 pc. 4950 RUB Buy

Vfend tablets p.p. 200mg 14pcs RUB 27829 Buy

Vfend 200 mg film-coated tablets 14 pcs. RUB 27829 Buy

Maria Kulkes Medical journalist About the author

Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!