Voricoz pills 200mg, 7pcs

Composition

Each film-coated tablet contains: Active ingredient: voriconazole (micronized) – 200 mg. Auxiliary substances: pregelatinized corn starch-99.00 mg, crospovidone-15.00 mg, mannitol-250.00 mg, magnesium stearate-6.00 mg, croscarmellose sodium-30.00 mg. Water-based film coating: Opadray white II (85F18422) (polyvinyl alcohol-4,8 mg, titanium dioxide-3,0 mg, macrogol 4000-2,424 mg, talc-1,776 mg) – 12 mg

Pharmacological action

Voriconazole is a broad-spectrum antifungal drug from the triazole group. The mechanism of action is related to the inhibition of 14α-sterol demethylation mediated by fungal cytochrome P450; this reaction is a key step in ergosterol biosynthesis. The accumulation of 14α-methylsterol correlates with the subsequent loss of ergosterol in fungal cell membranes, which determines the antifungal activity of voriconazole. Voriconazole was found to be more selective for fungal cytochrome P450 isoenzymes than for various mammalian cytochrome P450 enzyme systems. No positive relationship was found between the average, maximum and minimum values of voriconazole concentrations in blood plasma and the effectiveness of the drug in therapeutic studies, and this relationship was not studied in preventive studies. Pharmacodynamic and pharmacokinetic analysis of these clinical studies revealed a positive relationship between the concentration of voriconazole in blood plasma and deviations from the norm of biochemical parameters of liver function, as well as visual disturbances. In vitro voriconazole has a broad spectrum of antifungal action: It is active against Candida spp. (including strains of C. krusei resistant to fluconazole, and resistant strains of C. glabrata and C. albicans) and has a fungicidal effect against all studied strains of Aspergillus spp., as well as pathogenic fungi that have become relevant recently, including Scedosporium spp. or Fusarium spp., which are to a limited extent sensitive to existing antifungal agents. Clinical efficacy (with partial or complete response) of voriconazole has been demonstrated in infections caused by Aspergillus spp., including A. flavus, A. fumigatus, A. terreus, A. niger, A. nidulans, Candida spp., including strains of C. albicans, C. glabrata, C. krusei, C. parapsilosis, C. tropicalis, as well as against a limited number of strains of C. dubliniensis, C. inconspicua, C. guilliermondii, Scedosporium spp. (including S. apiospermum, S. prolificans) and Fusarium spp. Other fungal infections for which voriconazole was used (with partial or complete response) included isolated cases of infections caused by Alternaria spp., Blastomyces dermatitidis, Blastoschizomyces capitatus, Cladosporium spp., Coccidioides immitis, Conidiobolus coronatus, Cryptococcus neoformans, Exserohilum rostratum, Exophiala spinifera, Fonsecaea pedrosoi, Madurella mycetomatis, Paecilomyces lilacinus, Penicillium spp., including P. marneffei, Phialophora richardsiae, Scopulariopsis brevicaulis, and Trichosporon spp., including T. beigelii. In vitro activity of voriconazole was demonstrated against clinical strains of Acremonium spp., Alternaria spp., Bipolaris spp., Cladophialophora spp., and Histoplasma capsulatum. The growth of most strains was suppressed at voriconazole concentrations from 0.05 to 2 micrograms / ml. In vitro activity of voriconazole against Curvularia spp. and Sporothrix spp. was detected, but its clinical significance is unknown.

Indications

• esophageal candidiasis;
• serious fungal infections caused by Scedosporium spp. and Fusarium spp. ;
• other severe invasive fungal infections in case of intolerance or refractoriness to other drugs;
• invasive aspergillosis;
• candidemia in patients without neutropenia;
• severe invasive Candida infections (including Candida krusei);
• prevention of breakthrough fungal infections in patients with reduced function of the immune system, fever and neutropenia, high-risk (recipients of hematopoietic stem cell transplantation, patients with relapse of leukemia);
• prevention of invasive fungal infections in patients (adults and children older than 12 years) high-risk groups, such as recipients of hematopoietic stem cell transplantation.

Use during pregnancy and lactation

There is no sufficient information about the use of the drug in pregnant women. In experimental studies on animals, it was found that voriconazole in high doses has a toxic effect on reproductive function. The possible risk to the individual is unknown. Voriconazole should not be used during pregnancy unless the expected benefit to the mother outweighs the possible risk to the fetus. The elimination of voriconazole in breast milk has not been studied. Breast-feeding should be discontinued for the duration of the drug use. Women of reproductive age should use reliable methods of contraception during the entire period of treatment with Voricosis.

Contraindications

Hypersensitivity to voriconazole or other components of the drug. Concomitant use of voriconazole and the following drugs is contraindicated: substrates of the CYP3A4 isoenzyme – terfenadine, astemizole, cisapride, pimozide and quinidine; sirolimus; rifampicin, carbamazepine and long-acting barbiturates (phenobarbital); rifabutin; ritonavir in high doses (400 mg and above twice a day); efavirenz in doses of 400 mg and above once a day (with voriconazole in standard doses); ergot alkaloids (ergotamine, dihydroergotamine); St. John’s wort (inducer of cytochrome P 450 and P-glycoprotein) (see “Interaction with other drugs”). Voriconazole is contraindicated in children under 3 years of age (for this dosage form). Use caution in case of hypersensitivity to other medicinal products-derivatives of azoles. The drug is prescribed with caution in patients with severe hepatic or renal insufficiency. Voriconazole should be used with caution in patients with proarrhythmic conditions: congenital or acquired prolongation of the QT interval, cardiomyopathy, especially with heart failure, sinus bradycardia, the presence of symptomatic arrhythmia, concomitant use of drugs that cause prolongation of the QT interval. Caution should also be exercised when using voriconazole in patients with electrolyte disorders, such as: hypokalemia, hypomagnesemia and hypocalcemia.

Side effects

The most common adverse reactions are visual disturbances, abnormal liver function tests, fever, rash, vomiting, nausea, diarrhea, headache, peripheral edema, abdominal pain, and respiratory depression. Adverse reactions were usually mild to moderate. There was no clinically significant dependence of the drug’s safety on age, race, or gender.

Frequency assessment criteria: very often ≥ 10%; often ≥ 1% and

Cardiac disorders: often-supraventricular arrhythmia, tachycardia, bradycardia; infrequently-ventricular fibrillation, ventricular extrasystole, ventricular tachycardia, supraventricular tachycardia; rarely-pirouette-type arrhythmia, complete atrioventricular block, bundle branch block, nodal arrhythmias.

Vascular disorders: often-hypotension, phlebitis; infrequently-thrombophlebitis.

Hematopoietic and lymphatic system disorders: often-agranulocytosis, pancytopenia, thrombocytopenia, anemia; infrequently-bone marrow depression, leukopenia, lymphadenopathy, eosinophilia, disseminated intravascular coagulation syndrome.

From the nervous system: very often – headache; often-syncope, tremor, dizziness, convulsions, nystagmus, paresthesia, drowsiness, dizziness; infrequently – cerebral edema, encephalopathy, extrapyramidal disorder, peripheral neuropathy, ataxia, hypesthesia, dysgeusia (impaired taste perception); rarely – hepatic encephalopathy, Hyenne-Barre syndrome.

From the side of the visual organ: very often – visual disturbances (blurred vision, chromatopsy, photophobia); often – hemorrhage in the retina of the eye; infrequently-optic neuritis, edema of the optic disc, ocular crisis, scleritis, diplopia, blepharitis; rarely-atrophy of the optic nerve, corneal opacity.

Hearing and vestibular disorders: infrequently-vertigo, hypoacusia, tinnitus.

Respiratory, thoracic and mediastinal disorders: often-pulmonary edema, acute respiratory distress syndrome; very often-respiratory depression.

Gastrointestinal disorders: very often-nausea, vomiting, diarrhea, abdominal pain; often-cheilitis, dyspepsia, constipation; infrequently-duodenitis, glossitis, pancreatitis, tongue edema.

Renal and urinary tract disorders: often-acute renal failure, hematuria; infrequently-renal tubular necrosis, proteinuria, nephritis.

Skin and subcutaneous tissue disorders: very common – rash; often – exfoliative dermatitis, alopecia, pruritus, maculopapular rash, erythema; infrequently – toxic epidermal necrolysis, angioedema, erythema multiforme, psoriasis, allergic dermatitis, Stevens-Johnson syndrome, photosensitization, urticaria, purpura, papular rash, macular rash, eczema; rarely – pseudoporphyria, persistent drug – induced erythema; frequency unknown-cutaneous form of systemic lupus erythematosus.

Musculoskeletal and connective tissue disorders: often-back pain; infrequently-arthritis; frequency unknown-periostitis.

Endocrine system disorders: infrequently-adrenal cortical insufficiency, hypothyroidism, rarely-hyperthyroidism.

Metabolic and nutritional disorders: very often – peripheral edema, often-hypokalemia, hypoglycemia, hyponatremia (revealed in post-marketing studies).

Infections and infestations: often-sinusitis, gastroenteritis, gingivitis; infrequently-pseudomembranous colitis, lymphangitis, peritonitis.

Common disorders: very often – pyrexia; often-flu-like illness, chills, asthenia, chest pain, facial edema (periorbital edema, lip edema, mouth edema).

Immune system disorders: infrequently-allergic reactions; rarely-anaphylactoid reactions.

Disorders of the hepatobiliary system: very often – abnormal results of functional liver tests, increased activity of aspartate aminotransferase, alanine aminotransferase, alkaline phosphotase, gamma-glutamyltransferase, lactate dehydrogenase, hyperbilirubinemia; often-jaundice, cholestatic jaundice, hepatitis; infrequently-cholecystitis, cholelithiasis, liver enlargement, liver failure.

Mental disorders: often – hallucinations, depression, anxiety, insomnia, agitation, confusion.

Benign, malignant, and unspecified neoplasms (including cysts and polyps): frequency unknown-squamous cell carcinoma of the skin.

Studies: often-increased creatinine concentration in the blood, infrequently-prolongation of the QT interval on an electrocardiogram, increased urea concentration in the blood, increased cholesterol concentration in the blood.

Side effect when used in children

It was found that the undesirable effects of the drug in children aged 3 to 12 years are similar to those in adults. Children had a higher frequency of increased activity of liver enzymes. Post-marketing studies revealed the development of pancreatitis in children during voriconazole therapy, as well as more frequent occurrence of skin reactions.

Interaction

Concomitant use of voriconazole is contraindicated with the following medications St. John’s wort has a short initial inhibitory effect on the metabolism of voriconazole, followed by its activation. Concomitant use of voriconazole and St. John’s wort is contraindicated (see section “Contraindications”). The concentration of voriconazole in blood plasma is significantly reduced when used simultaneously with the following drugs Rifampicin (600 mg 1 time per day) reduces the Cmax and AUCt of voriconazole by 93% and 96%, respectively. Concomitant use of voriconazole and rifampicin is contraindicated (see section “Contraindications”). Ritonavir. Taking ritoiavir (400 mg every 12 hours) reduced the Cmax and AUCt of voriconazole when taken orally by an average of 66% and 82%, respectively. Taking ritoiavir (100 mg every 12 hours) reduced the Cmax and AUCt of voriconazole when taken orally by an average of 24% and 39%, respectively. Repeated oral use of voriconazole was found to have no significant effect on the steady-state Cmax and AUCt of ritoiavir, taken at a dose of 400 mg every 12 hours. At the same time, a steady decrease in Cmax and AUCt by 25% and 13%, respectively, was observed when taking ritoiavir at a dose of 100 mg every 12 hours. Concomitant use of voriconazole and ritonavir (400 mg every 12 hours) is contraindicated (see section “Contraindications”). Concomitant use of voriconazole and ritoiavir at a dose of 100 mg every 12 hours should be avoided. It is highly probable that carbamazepine and long-acting barbiturates (phenobarbital) significantly reduce the concentration of voriconazole in blood plasma. Concomitant use of voriconazole with carbamazepine and long-acting barbiturates is contraindicated (see section “Contraindications”). Given the insignificant pharmacokinetic interaction, no dose adjustment is required for the following drugs: Cimetidine (400 mg twice daily) causes an increase in Cmax and AUCt of voriconazole by 18% and 23%, respectively. No dose adjustment of voriconazole is required. Ranitidine (150 mg twice daily) does not significantly affect the Cmax and AUCt of voriconazole. Erythromycin (1 g twice daily) and azithromycin (500 mg once daily) do not significantly affect the Cmax and AUCt of voriconazole. The effect of voriconazole on the metabolism of erythromycin or azithromycin is unknown. No dose adjustment is required. Concomitant use of voriconazole with the following medications is contraindicated: Terfenadine, astemizole, cisapride, pimozide and quinidine. Concomitant use of voriconazole with these drugs is contraindicated, as it can lead to an increase in their concentration in blood plasma. This, in turn, can cause prolongation of the QT interval and, in rare cases, lead to the development of ventricular fibrillation/flutter (see the section “Contraindications”). Sirolimus. Voriconazole increases the Cmax and AUCt of sirolimus (2 mg once) by 556% and 1014%, respectively. Concomitant use of voriconazole and sirolimus is contraindicated (see section “Contraindications”). It is highly probable that voriconazole can cause an increase in the concentration of ergot alkaloid preparations (ergotamine and dihydroergotamine) in blood plasma and the development of ergotism. Concomitant use of ergot alkaloids with voriconazole is contraindicated (see section “Contraindications”). Interaction with voriconazole may lead to an increase in the plasma concentration of the following drugs Cyclosporine. In stable kidney transplant patients, voriconazole increases the Cmax and AUCt of cyclosporine by at least 13% and 70%, respectively. When prescribing voriconazole to patients receiving cyclosporine, it is recommended to reduce the dose of cyclosporine by half and monitor its concentration in blood plasma. Tacrolimus. Voriconazole increases the Cmax and AUCt of tacrolimus (0.1 mg / kg once) by 117% and 221%, respectively. When prescribing voriconazole to patients receiving tacrolimus, it is recommended to reduce the dose of the latter to one-third and monitor its concentration in blood plasma. Methadone. Repeated oral use of voriconazole increases the Cmax and AUCt of pharmacologically active R-methadone by 31% and 47%, respectively, in patients receiving a maintenance dose of methadone (30-100 mg per day). An increase in the concentration of methadone in the blood plasma leads to toxic effects, including prolongation of the QT interval. When using voriconazole and methadone at the same time, it is necessary to carefully monitor the manifestation of undesirable and toxic effects. If necessary, the dose of methadone can be reduced. Short-acting narcotic analgesics. Continuous oral use of voriconazole increases the AUC of alfentanil by 6 times in a single dose. Concomitant use of voriconazole and alfentanil or other short-acting narcotic analgesics, its structural analogues (for example, sufentanil) should provide for a reduction in the dose of the latter. Since the T1 / 2 of alfentanil increases 4-fold when co-administered with voriconazole, careful monitoring of adverse events associated with the use of narcotic analgesics is necessary, including longer monitoring of respiratory function. Fentanyl. Concomitant use of voriconazole and fentanyl in a single dose of 5 mcg/kg intravenously increases the AUC of fentanyl by an average of 1.4 times. If necessary, the dose of fentanyl should be reduced. Oxycodone. Concomitant oral use of voriconazole and oxycodone in a single dose of 10 mg increases the Cmax and AUC of oxycodone by 1.7 times and 3.6 times. T1 / 2 of oxycodone increases 2-fold. Adverse events should be carefully monitored. It may be necessary to reduce the dose of oxycodone in combination with voriconazole. Warfarin. Concomitant use of voriconazole (300 mg twice daily) with warfarin (30 mg once daily) was associated with a 93% increase in the maximum prothrombin time. When warfarin and voriconazole are used simultaneously, it is recommended to monitor prothrombin time. Other oral anticoagulants, such as phenprocumone, acenocoumarol. Voriconazole may cause an increase in the concentration of coumarin derivatives in blood plasma and prothrombin time. When used together, it is necessary to monitor prothrombin time at short intervals and adjust the dose of anticoagulants accordingly. Derivatives of sulfonylureas. Voriconazole may increase the concentration of sulfonylurea derivatives (tolbutamide, glipizide and glyburide) in the blood plasma and cause hypoglycemia. When using voriconazole concomitantly with these drugs, it is necessary to carefully monitor the concentration of glucose in the blood. Statins. Voriconazole may cause an increase in plasma statin concentrations. With simultaneous use, it is recommended to evaluate the feasibility of adjusting the dose of statins. Increased statin concentrations are sometimes accompanied by the development of rhabdomyolysis. Benzodiazepines. Voriconazole may cause an increase in plasma concentrations of benzodiazepines (midazolam, triazolam, alprazolam) and the development of prolonged sedation. With concomitant use of voriconazole and benzodiazepines, it is recommended to evaluate the feasibility of adjusting the dose of benzodiazepines. Periwinkle alkaloids. Voriconazole can increase the content of periwinkle alkaloids (vincristine and vinblastine) in blood plasma and cause neurotoxicity. When using voriconazole and periwinkle alkaloids simultaneously, it is recommended to evaluate the feasibility of adjusting the dose of periwinkle alkaloids. NSAIDs. Voriconazole increases the Cmax and AUC of ibuprofen (400 mg once) by 20% and 100%, respectively, and the Cmax and AUC of diclofenac (50 mg once) by 114% and 78%, respectively.In the case of concomitant use of voriconazole and NSAIDs, patients should be monitored for possible toxic effects and, if necessary, adjust the dose of NSAIDs. When voriconazole is co-administered with the following drugs, no significant pharmacokinetic interaction was detected, so no dose adjustment is required. Prednisone. Voriconazole increases the Cmax and AUCt of prednisone (60 mg once) by 11% and 34%, respectively. No dose adjustment is required. Digoxin. Voriconazole has no significant effect on Cmax and AUC of digoxin (0.25 mg once daily). Mycophenolic acid. Voriconazole does not affect the Cmax and AUCt of mycophenolic acid (1 g once). Two-way interaction. Phenytoin. Concomitant use of voriconazole and phenytoin should be avoided unless the expected benefit outweighs the possible risk. Phenytoin (300 mg once daily) reduces the Cmax and AUCt of voriconazole by 49% and 69%, respectively. Voriconazole (400 mg once daily) increases the Cmax and AUCt of phenytoin (300 mg once daily) by 67% and 81%, respectively. When using phenytoin concomitantly with voriconazole, it is recommended to monitor the concentration of phenytoin in blood plasma. Phenytoin can be used together with voriconazole if the maintenance dose of the latter is increased from 200 to 400 mg every 12 hours orally (from 100 to 200 mg every 12 hours orally). Omeprazole (40 mg once daily) increases the Cmax and AUCt of voriconazole by 15% and 41%, respectively. Dose adjustment of voriconazole is not recommended. Voriconazole increases the Cmax and AUCt of omeprazole by 116% and 280%, respectively. When prescribing voriconazole to patients receiving omeprazole, the dose of the latter is recommended to be halved. Voriconazole may also inhibit the metabolism of other proton pump inhibitors that are substrates of the CYP2C19 isoenzyme. Oral contraceptives. Concomitant use of voriconazole and oral contraceptives (1 mg of norethisterone and 0.035 mg of ethinyl estradiol 1 time per day) leads to an increase in Cmax and AUCt of norethisterone by 15% and 53%, respectively, and ethinyl estradiol-by 36% and 61%, respectively. The Cmax and AUCt of voriconazole increased by 14% and 46%, respectively. Since the ratio between norethisterone and ethinyl estradiol remains approximately the same when interacting with voriconazole, it can be assumed that their contraceptive activity does not change. In the case of concomitant use of voriconazole and oral contraceptives, monitoring should be carried out to identify possible undesirable effects. Low-dose oral contraceptives have not been studied. Indinavir (800 mg 3 times a day) does not significantly affect the Cmax and AUCt of voriconazole. Voriconazole does not significantly affect the Cmin, Cmax and AUCt of indinavir (800 mg 3 times a day). Other HIV protease inhibitors. Voriconazole can inhibit the metabolism of HIV protease inhibitors: saquinavir, amprenavir and nelfinavir. In turn, HIV protease inhibitors can inhibit the metabolism of voriconazole. If voriconazole is co-administered with HIV protease inhibitors, patients should be monitored for possible toxic effects. Efavirenz. At steady state, efavirenz (400 mg once daily) reduces the steady-state Cmax and AUCt of voriconazole by an average of 61% and 77%, respectively. Voriconazole at steady state increases the steady-state Cmax and AUCt of efavirenz by an average of 38% and 44%, respectively. Standard doses of voriconazole and efavirenz (400 mg once daily) are contraindicated. Concomitant use is possible if the maintenance dose of voriconazole is increased to 400 mg twice daily, and the efavirenz dose is reduced to 300 mg once daily. If voriconazole therapy is discontinued, the initial efavirenz dose should be restored. Other non-nucleoside reverse transcriptase inhibitors. Delavirdine may inhibit the metabolism of voriconazole. Nevirapine may induce voriconazole metabolism. Voriconazole may inhibit the metabolism of non-nucleoside reverse transcriptase inhibitors. When voriconazole is co-administered with non-nucleoside reverse transcriptase inhibitors, patients should be monitored for possible toxic effects. Fluconazole (200 mg once a day). Concomitant oral use of voriconazole and fluconazole leads to an increase in Cmax and AUCt of voriconazole by 57% and 79%, respectively. Changes in the Cmax and AUCt of fluconazole were not detected. A suitable dosage and/or frequency adjustment regimen for voriconazole and fluconazole has not been established. In the event that voriconazole is used after fluconazole, careful monitoring of adverse reactions associated with voriconazole is recommended. Everolimus. Interaction has not been studied, however, concomitant use is not recommended, as voriconazole is expected to significantly increase plasma concentrations of everolimus. At the moment, there is not enough information available to recommend correction of the dosage regimen. Concomitant use of voriconazole is contraindicated with the following medications Rifabutin (300 mg once daily) reduces the Cmax and AUCt of voriconazole (200 mg twice daily) by 69% and 78%, respectively. With simultaneous use of rifabutin, Cmax and AUCt of voriconazole at a dose of 350 mg 2 times a day were 96% and 68% of the indicators when using only voriconazole at a dose of 200 mg 2 times a day. When using voriconazole at a dose of 400 mg 2 times a day, Cmax and AUCt, respectively, are 104% and 87% higher than when using voriconazole at a dose of 200 mg 2 times a day. Voriconazole 400 mg twice daily increases the Cmax and AUCt of rifabutin by 195% and 331%, respectively. Concomitant use of voriconazole and rifabutin is contraindicated (see section “Contraindications”).

How to take, course of use and dosage

The drug VORIKOZ (micronized) is prescribed orally,1 hour before meals or 1 hour after meals. The tablet should be swallowed whole, without chewing, with a sufficient amount of water.

Before starting therapy, it is necessary to correct such electrolyte disturbances as hypokalemia, hypomagnesemia and hypocalcemia.

For adults, the drug is prescribed on the first day at the recommended saturating dose, so that on the first day of therapy the concentration of voriconazole in blood plasma is close to equilibrium.

Overdose

Treatment: the antidote of voriconazole is not known, if necessary, symptomatic therapy is carried out, gastric lavage is possible. Voriconazole is eliminated on hemodialysis with a clearance of 121 ml / min. In case of overdose, hemodialysis is indicated.

Form of production

Film-coated tablets

Storage conditions

Store in a dry place, protected from light, at a temperature of 8 °C to 25 °C. Keep out of reach of children.

Shelf

life is 3 years.

Active ingredient

Voriconazole

Conditions of release from pharmacies

By prescription

Dosage form

Tablets