Voriconazole

Voriconazole

This product is used to treat invasive aspergillosis, severe invasive candidiasis infections resistant to fluconazole (including Candida krusei), and severe fungal infections caused by Actinomyces and Fusarium. It is mainly used for patients with progressive, life-threatening immune damage.

Oral administration: If the patient's treatment response is poor, the oral maintenance dose can be increased to 300 mg twice a day; the dose for patients weighing less than 40 kg is adjusted to 150 mg twice a day. If the patient cannot tolerate the above higher doses, the oral maintenance dose can be reduced by 50 mg each time, gradually reduced to 200 mg twice a day (reduced to 100 mg twice a day for patients weighing less than 40 kg). Medication for the elderly: No dose adjustment is required when the elderly use this product. Medication for patients with renal impairment: When patients with moderate to severe renal impairment (creatinine clearance < 50 mL/min) use this product, the excipient sodium sulfobutyl beta-cyclodextrin (SBECD) may accumulate. Such patients should choose oral administration unless the benefits of intravenous preparations outweigh the risks. These patients must closely monitor serum creatinine levels during intravenous administration, and if there is an abnormal increase, they should consider switching to oral administration. Voriconazole can be cleared by hemodialysis, with a clearance rate of 121 mL/min. Only a small amount of drug can be removed by 4 hours of hemodialysis, and no dose adjustment is required. The excipient of intravenous preparation, sulfobutyl beta-cyclodextrin sodium (SBECD), has a clearance rate of 55 mL/min in hemodialysis. Use in patients with impaired liver function: No dose adjustment is required for patients with acute liver damage (increased alanine aminotransferase ALT/GOT and aspartate aminotransferase AST/GST), but liver function should continue to be monitored to observe whether there is further increase. It is recommended that the loading dose of voriconazole remain unchanged for patients with mild to moderate cirrhosis (Child-Pugh A and B), but the maintenance dose is halved. There are currently no studies on the use of this product in patients with severe cirrhosis (Child-Pugh C). There are reports that this product is associated with abnormal increases in liver function tests and signs of liver damage (such as jaundice), so the pros and cons must be weighed when using this product in patients with severe liver dysfunction. Patients with impaired liver function must be closely monitored for drug toxicity when using this product. Pediatric use: The safety and effectiveness of voriconazole in children under 12 years old have not been established. A total of 22 patients with invasive aspergillosis aged 12-18 years were enrolled in the therapeutic study and given a maintenance dose of voriconazole, 4 mg/kg every 12 hours. Twelve patients (55%) responded to the treatment. Adolescents (12-16 years): In the therapeutic study, the pharmacokinetic properties of voriconazole in adolescents were rarely studied.

Overall: The most common adverse events in the treatment trials were visual disturbances, fever, rash, nausea, vomiting, diarrhea, headache, sepsis, peripheral edema, abdominal pain, and respiratory dysfunction. The most common adverse events related to treatment that led to discontinuation included increased liver function test values, rash, and visual disturbances. Discussion of adverse reactions: The data in the following table are from 1493 patients who participated in voriconazole treatment studies. It represents a different population, including immunocompromised patients, such as patients with hematological malignancies, HIV patients, and patients with non-neutropenic neutrophils. But it does not include healthy volunteers, patients who were treated for compassionate reasons and not participating in treatment studies. Among these patients, 62% were male, with an average age of 45.1 years (12-90 years, including 49 patients aged 12-18 years), 81% were white, and 9% were black. 561 patients received voriconazole for more than 12 weeks, and 136 patients received more than 6 months. The following table summarizes adverse events with an incidence greater than 1% in all treatment studies, as well as significant events with an incidence greater than 1%. In Study 307/602, 381 patients with acute invasive aspergillosis were treated with voriconazole (196 patients) and amphotericin B (185 patients) followed by other licensed antifungal agents. Study 305 evaluated the efficacy of oral voriconazole (200 patients) and oral fluconazole (191 patients) in the treatment of esophageal candidiasis. Laboratory abnormalities in these studies are discussed later in the Clinical Trials Values section. Treatment-emergent adverse events (including adverse events with an incidence greater than 1% in all treatment studies, as well as significant events with an incidence greater than 1% that may be drug-related or unclear): *Other marketed antifungal treatments were administered after amphotericin B. Visual disturbances: Visual disturbances associated with voriconazole are common. In clinical trials, approximately 30% of patients experienced visual changes, enhanced vision, blurred vision, color vision changes and/or photophobia. Visual impairment is usually mild and rarely leads to discontinuation. Visual impairment may be related to higher blood concentrations and/or doses. Although the site of action of voriconazole seems to be mainly limited to the retina, its mechanism of action remains unclear. In a study, the effects of 28 days of voriconazole treatment on retinal function were studied in healthy volunteers, and it was found that this product can reduce the amplitude of retinal electrographic waveforms, narrow the visual field and change color vision. Electroretinograms are usually used to detect the current in the retina. Electroretinograms, visual fields and color vision return to normal 14 days after discontinuation of the drug. The effects of voriconazole on vision can occur early in the course of medication and persist throughout the course of medication. There is evidence that visual impairment is related to multiple doses. Skin reactions: In clinical trials, skin reactions were common in the voriconazole treatment group. The mechanism of these skin adverse events remains unclear. However, these patients usually also have other serious underlying diseases and need to receive multiple treatments at the same time. In clinical trials, the incidence of voriconazole-related rash was 6% (86/1493). Most rashes were mild to moderate, including Stevens-Johnson syndrome, toxic epidermal necrosis, and erythema multiforme. Once a patient develops a rash, he or she must be closely observed. If the skin lesions worsen, the drug must be discontinued. Photosensitivity has also been reported, and photosensitivity reactions are more common in patients receiving long-term treatment. Severe skin reactions are extremely rare. It is recommended to avoid strong direct sunlight during voriconazole treatment. Other less common adverse events: The adverse events listed below have an incidence of 1% in all patients using voriconazole (including healthy volunteers, etc., N=2090). These adverse events include those that cannot be ruled out as being related to voriconazole or those that help doctors manage the risks of patients taking the drug, but do not include the adverse events listed in the table above, nor do they include all adverse events reported in clinical trials. Systemic Reactions: Abdominal distension, anaphylactic reaction, anaphylactoid reaction, ascites, weakness, back pain, cellulitis, edema, facial edema, flank pain, flu-like symptoms, graft-versus-host reaction, granuloma, infection, bacterial infection, fungal infection, injection site pain, injection site infection/inflammation, mucosal dysfunction, multi-organ failure, pain, pelvic pain, peritonitis, sepsis, substernal chest pain. Cardiovascular: Atrial arrhythmia, atrial fibrillation, complete atrioventricular block, bigeminy, bradycardia, bundle branch block, cardiomegaly, cardiomyopathy, cerebral hemorrhage, cerebral ischemia, cerebrovascular accident, congestive heart failure, deep thrombophlebitis, endocarditis, extrasystoles, cardiac arrest, myocardial infarction, nodal arrhythmia, palpitations, phlebitis, postural hypotension, pulmonary embolism, QT interval prolongation, supraventricular tachycardia, syncope, thrombophlebitis, vasodilation, ventricular arrhythmia, ventricular fibrillation, ventricular tachycardia (including torsade de pointes). Digestive system: anorexia, cheilitis, cholecystitis, cholelithiasis, constipation, duodenal ulcer perforation, duodenitis, indigestion, dysphagia, esophageal ulcer, esophagitis, flatulence, gastroenteritis, gastrointestinal bleeding, gamma;GT/LDH increased, gingivitis, glossitis, gingival bleeding, gingival hyperplasia, hematemesis, hepatic coma, liver failure, hepatitis, intestinal perforation, intestinal ulcer, hepatomegaly, melena, oral ulcer, pancreatitis, parotid enlargement, periodontitis, proctitis, pseudomembranous enteritis, rectal dysfunction, rectal bleeding, gastric ulcer, gastritis, tongue enlargement. Endocrine: adrenal insufficiency, diabetes insipidus, hyperthyroidism, hypothyroidism. Blood and Lymph: Agranulocytosis, anemia (macrocytic anemia, megaloblastic anemia, microcytic anemia, normocytic anemia), aplastic anemia, hemolytic anemia, prolonged bleeding time, cyanosis, disseminated intravascular coagulation, ecchymoses, eosinophilia, hypervolemia, lymphadenopathy, lymphangitis, bone marrow suppression, petechiae, purpura, splenomegaly, thrombotic thrombocytopenic purpura. Nutrition and Metabolism: Proteinuria, increased urea nitrogen, increased creatinine phosphokinase, edema, decreased glucose tolerance, hypercalcemia, hypercholesterolemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hyperuricemia, hypocalcemia, hypoglycemia, hyponatremia, hypophosphatemia, uremia. Musculoskeletal: Arthralgia, arthritis, bone gangrene, bone pain, calf cramps, myalgia, myasthenia, myopathy, osteomalacia, osteoporosis. Nervous system: abnormal dreams, acute brain syndrome, agitation, akathisia, amnesia, anxiety, ataxia, cerebral edema, coma, mental confusion, convulsions, delirium, dementia, depersonalization, depression, diplopia, encephalitis, encephalopathy, euphoria, extrapyramidal syndrome, grand mal seizures, Guillain-Barré syndrome, hypertonia, hypoesthesia, insomnia, increased intracranial pressure, decreased libido, neuralgia, neuropathy, nystagmus, eye cyclotorsion crisis, paresthesia, psychosis, somnolence, suicidal tendencies, tremor, vertigo. Respiratory system: increased cough, dyspnea, epistaxis, hemoptysis, hypoxia, pulmonary edema, pharyngitis, pleural effusion, pneumonia, respiratory dysfunction, respiratory distress syndrome, respiratory tract infection, rhinitis, sinusitis, voice changes. Skin and Appendages: Alopecia, angioedema, contact dermatitis, discoid lupus erythematosus, eczema, erythema multiforme, exfoliative dermatitis, mixed drug eruption, furunculosis, herpes simplex, melanosis, photosensitivity skin reaction, psoriasis, skin discoloration, skin disease, dry skin, Stevens-Johnson syndrome, sweating, toxic epidermal necrosis, urticaria. Special Senses: Accommodation abnormalities, blepharitis, color blindness, conjunctivitis, corneal opacities, deafness, earache, eye pain, dry eyes, keratitis, keratoconjunctivitis, mydriasis, night blindness, optic atrophy, optic neuritis, otitis externa, papilledema, retinal hemorrhage, retinitis, scleritis, loss of taste, taste abnormalities, uveitis, tinnitus, visual field loss. Urogenital system: anuria, atrophic eggs, decreased creatinine clearance, dysmenorrhea, dysuria, epididymitis, diabetes, hemorrhagic cystitis, hematuria, hydronephrosis, impotence, renal pain, renal tubular necrosis, irregular uterine bleeding, nephritis, nephropathy, oliguria, scrotal edema, urinary incontinence, urinary retention, urinary tract infection, uterine bleeding, vaginal bleeding. Clinical laboratory test values In clinical trials, the total incidence of clinically significant transaminase abnormalities in the voriconazole group was 13.4% (200/1493). Abnormal liver function tests may be related to higher blood drug concentrations and/or doses. The vast majority of patients can be relieved by continuing to take the drug according to the original dosing regimen, or by adjusting the dose and continuing to take the drug (including stopping the drug). In patients using voriconazole, severe hepatotoxicity such as jaundice rarely occurs, and hepatitis and fatal liver failure are even rarer. Most of the patients with the above adverse events are accompanied by other serious underlying diseases. Liver function should be checked at the beginning and during treatment with voriconazole. If liver function abnormalities occur during treatment, close monitoring is required to prevent more serious liver damage. Treatment should include laboratory evaluation of liver function (especially liver function tests and bilirubin). If clinical symptoms and signs are consistent with the development of liver disease and can be attributed to voriconazole, the drug must be discontinued. There are reports that acute renal failure may occur in critically ill patients when using this product. When this product is used in combination with nephrotoxic drugs and when patients have other underlying diseases, renal impairment may occur. Therefore, renal function needs to be monitored when using this product, including laboratory tests, especially blood creatinine values.

This product is contraindicated in patients with a known history of hypersensitivity to voriconazole or any of the excipients. Warning Visual impairment: The effect of voriconazole on visual function when the treatment course exceeds 28 days is unknown. If treatment is continued for more than 28 days, visual function, including visual acuity, visual range, and color vision, should be monitored. Hepatotoxicity: In clinical trials, serious liver adverse reactions (including hepatitis, cholestasis, and fatal fulminant hepatic failure) were uncommon in the voriconazole treatment group. Hepatotoxic reactions have been reported mainly in patients with severe underlying diseases (mainly hematological malignancies). Liver reactions, including hepatitis and jaundice, can occur in patients without other established risk factors. Abnormal liver function usually improves after discontinuation of the drug. Monitoring liver function: Liver function should be checked before and during treatment with voriconazole. Patients must routinely monitor liver function at the beginning of treatment and when abnormal liver function occurs during treatment to prevent more serious liver damage. Monitoring should include laboratory tests of liver function (especially liver function tests and bilirubin). If clinical symptoms and signs are consistent with the development of liver disease, discontinuation of the drug should be considered. Galactose intolerance Voriconazole tablets contain lactose. People with rare, congenital galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not use this product.

This product is contraindicated for use with CYP3A4 substrates, terfenadine, astemizole, cisapride, pimozide or quinidine, because this product can increase the blood concentration of the above drugs, resulting in prolonged Q-T interval and occasional torsade de pointes. This product is contraindicated for use with rifampicin, carbamazepine and phenobarbital, the latter of which can significantly reduce the blood concentration of this product. This product cannot be used in combination with ergot alkaloids (ergotamine, dihydroergotamine). Ergot alkaloids are substrates of CYP3A4. When the two are used together, the increased blood concentration of ergot drugs can lead to ergot poisoning. When sirolimus is used in combination with voriconazole, the blood concentration of the former may increase significantly, so these two drugs cannot be used at the same time. This product is contraindicated for use with ritonavir (400 mg each time, once every 12 hours). When healthy subjects were given ritonavir (400 mg each time, once every 12 hours) and voriconazole at the same time, the blood concentration of voriconazole was significantly reduced. Ritonavir 100 mg each time, once every 12 hours is used to inhibit CYP3A, thereby increasing the concentration of other antiretroviral drugs, but the effect of this dosing regimen on the concentration of voriconazole has not been studied. This product is prohibited from being used simultaneously with efavirenz. When the two are used simultaneously, the blood concentration of voriconazole is significantly reduced, while the blood concentration of efavirenz is significantly increased. This product is prohibited from being used simultaneously with rifabutin. When the two are used together, the blood concentration of voriconazole is significantly reduced, while the blood concentration of rifabutin is significantly increased. Unless otherwise specified, drug interaction studies were conducted in healthy male volunteers. Multiple doses were administered, 200 mg orally each time, twice a day, until steady-state concentrations were reached. These research results are also of reference significance for other populations and other routes of administration. This section describes the effects of other drugs on voriconazole, the effects of voriconazole on other drugs, and the interactions between the two drugs. The first and second parts of the interaction are described in the following order: prohibited co-use; dose adjustment and close clinical and/or biological monitoring are required when co-use; and finally, no obvious pharmacokinetic interaction, but may be beneficial to clinical treatment. Effects of other drugs on voriconazole Voriconazole is metabolized by cytochrome P450 isoenzymes, including CYP2C19, CYP2C9 and CYP3A4. Inhibitors or inducers of these isoenzymes can increase or decrease the blood concentration of voriconazole, respectively. Rifampicin (CYP450 inducer): When co-administered with rifampicin (600 mg once a day), the Cmax (peak blood concentration) and AUC (area under the concentration-time curve during the dosing interval) of voriconazole were reduced by 93% and 96%, respectively. Therefore, it is prohibited to co-administer this product with rifampicin. Carbamazepine and phenobarbital (potential CYP450 inducers): Although not studied, carbamazepine and phenobarbital may significantly reduce the plasma concentration of voriconazole, so this product is contraindicated for co-administration with these two drugs. Cimetidine (nonspecific CYP450 inhibitor and can increase gastric acid pH): When co-administered with cimetidine (400 mg twice daily), the Cmax and AUC of voriconazole increased by 18% and 23%, respectively. No dose adjustment of this product is required for co-administration of the two. Ranitidine (increases gastric acid pH): Ranitidine (150 mg twice daily) had no significant effect on the Cmax and AUC of voriconazole. Macrolide antibiotics: Erythromycin (CYP3A4 inhibitor, 1 g twice daily) and azithromycin (500 mg once daily) had no significant effect on the Cmax and AUC of voriconazole. Effects of voriconazole on other drugs Voriconazole inhibits the activity of cytochrome P450 isoenzymes, including CYP2C19, CYP2C9 and CYP3A4. Therefore, this product may increase the blood concentration of drugs metabolized by CYP45O isoenzymes. Terfenadine, astemizole, cisapride, pimozide and quinidine (CYP3A4 substrates): Although not studied, voriconazole is contraindicated for co-administration with terfenadine, astemizole, cisapride, pimozide or quinidine. Because this product can increase the blood concentration of the above drugs, resulting in prolonged Q-T interval and occasional torsade de pointes ventricular tachycardia. Sirolimus (CYP3A4 substrate): When co-administered with voriconazole, the Cmax and AUC of sirolimus (single dose of 2g) increased by 556% and 1014%, respectively. Therefore, the co-administration of these two drugs is contraindicated. Ergot alkaloids (CYP3A4 substrates): Although not studied, the blood concentration of ergot alkaloids (ergotamine and dihydroergotamine) may increase when used in combination with voriconazole, resulting in ergot poisoning. Therefore, the combination of voriconazole and ergot alkaloids is contraindicated. Cyclosporine (CYP3A4 substrate): In stable renal transplant patients, voriconazole can increase the Cmax and AUC of cyclosporine by at least 13% and 70%, respectively. When patients who have been treated with cyclosporine start using this product, it is recommended that their cyclosporine dose be halved and the blood concentration of cyclosporine be closely monitored. Increased cyclosporine concentrations can cause renal toxicity. After discontinuation of this product, the concentration of cyclosporine still needs to be closely monitored, and the dose of cyclosporine can be increased if necessary. Tacrolimus (CYP3A4 substrate): When used in combination with voriconazole, the Cmax and AUC of tacrolimus (single dose 0.1 mg/kg) increased by 117% and 221%, respectively. When patients who have been treated with tacrolimus begin to use this product, it is recommended that the dose of tacrolimus be reduced to 1/3 of the original dose and blood concentrations be closely monitored. Increased tacrolimus concentrations can cause renal toxicity. After discontinuation of this product, the concentration of tacrolimus still needs to be closely monitored, and the dose of tacrolimus can be increased if necessary. Oral anticoagulants: Warfarin (CYP2C9 substrate): When voriconazole (twice a day, 300 mg each time) is used in combination with warfarin (single dose 30 mg), the prothrombin time can be extended by up to 93%. Therefore, when the two are used in combination, it is recommended to closely monitor the prothrombin time. Other oral anticoagulants, such as phenylprocoumon and acenocoumarol (CYP2C9 and CYP3A4 substrates): Although not studied, the blood concentration of coumarin may increase when coumarins are used in combination with voriconazole, thereby prolonging the prothrombin time. If patients are taking voriconazole and coumarin preparations at the same time, the prothrombin time needs to be closely monitored and the dose of the anticoagulant should be adjusted accordingly. Sulfonylureas (CYP2C9 substrates): Although not studied, voriconazole may increase the blood concentration of sulfonylurea drugs (such as tolbutamide, glipizide, glyburide) when used simultaneously, thus causing hypoglycemia. Therefore, close monitoring of blood sugar is recommended when the two are used in combination. Statins (CYP3A4 substrates): Although not studied clinically, in vitro tests (human liver microsomes) have shown that voriconazole inhibits the metabolism of lovastatin. Therefore, the co-administration of voriconazole and statins may increase the blood concentration of statins metabolized by CYP3A4. Increased blood concentrations of statins may cause rhabdomyolysis, and it is recommended that the dose of statins should be adjusted when the two are co-administered. Benzodiazepines (CYP3A4 substrates): Although not clinically studied, voriconazole has been shown to inhibit the metabolism of midazolam in vitro (liver microsomes). Therefore, voriconazole may increase the blood concentration of benzodiazepines (midazolam and triazolam) metabolized by CYP3A4 and prolong the duration of sedation. It is recommended to adjust the dose of benzodiazepines when the two drugs are co-administered. Vinca alkaloids (CYP3A4 substrates): Although not studied, the blood concentrations of vinca alkaloids (vincristine and vinblastine) may still increase when used in combination with voriconazole, resulting in neurotoxicity. Prednisone (CYP3A4 substrate): When used in combination with voriconazole, the Cmax and AUC of prednisone (single dose 60 mg) increased by 11% and 34%, respectively. No dose adjustment is required when the two are used in combination. Digoxin (P-glycoprotein-mediated transport): Voriconazole has no significant effect on the Cmax and AUC of digoxin (0.25 mg once a day). Mycophenolic acid (UDP-glucuronyltransferase substrate): Voriconazole has no significant effect on the Cmax and AUCtau of mycophenolic acid (1g single dose). Drug interactions Phenytoin (CYP2C9 substrate and strong inducer of CYP450): The simultaneous use of phenytoin and voriconazole should be avoided as much as possible unless the benefits outweigh the risks after weighing them. Phenytoin once a day, 300 mg each time, can reduce the Cmax and AUC of voriconazole by 49% and 69% respectively; voriconazole twice a day, 400 mg each time (see Dosage and Administration) can increase the Cmax and AUC of phenytoin (once a day, 300 mg each time) by 67% and 81% respectively. Therefore, when the two are used together, it is recommended to closely monitor the blood concentration of phenytoin. When used in combination with phenytoin, the maintenance dose of voriconazole needs to be appropriately adjusted. For oral administration, the dose of voriconazole is adjusted from 200 mg twice a day to 400 mg twice a day; if the patient weighs less than 40 kg, the dose is increased from 100 mg twice a day to 200 mg twice a day. For intravenous infusion, the dose is adjusted to 5 mg/kg twice a day. See Dosage and Administration. Rifabutin (CYP450 inducer): Avoid the combination of rifabutin and voriconazole unless the benefits outweigh the risks. When rifabutin (300 mg once daily) and voriconazole (200 mg twice daily) are used simultaneously, the Cmax and AUC of voriconazole are reduced by 69% and 78%, respectively. When voriconazole is administered twice daily, 350 mg each time, and is co-administered with rifabutin, its Cmax and AUC are 96% and 68% of those when it is used alone (200 mg twice daily), respectively. When voriconazole is administered twice daily, 400 mg each time, and is co-administered with rifabutin, its Cmax and AUC are 104% and 87% higher than those when it is used alone (200 mg twice daily), respectively; at the same time, the Cmax and AUC of rifabutin are increased by 195% and 331%, respectively. When rifabutin is used simultaneously with voriconazole, it is recommended to increase the maintenance dose of voriconazole. For oral administration, the dose is adjusted from 200 mg twice a day to 350 mg twice a day; if the patient weighs less than 40 kg, the dose is increased from 100 mg twice a day to 200 mg twice a day. For intravenous infusion, the dose is adjusted to 5 mg/kg twice a day. And monitor complete blood counts and adverse events of rifabutin (such as uveitis). Omeprazole (CYP2C19 inhibitor, CYP2C19 and CYP3A4 substrate): When used simultaneously with omeprazole (single dose of 40 mg per day), the Cmax and AUC of voriconazole increased by 15% and 41%, respectively. No dose adjustment of voriconazole is required. When used in combination with voriconazole, the Cmax and AUC of omeprazole increased by 116% and 280%, respectively. Therefore, when patients who are taking omeprazole start taking voriconazole, it is recommended to halve the dose of omeprazole. Voriconazole also inhibits the metabolism of other proton pump inhibitor drugs that are CYP2C19 substrates. Indinavir: (CYP3A4 substrate and inhibitor): The Cmax, Cmin (blood trough concentration) and AUC of voriconazole, as well as the Cmax and AUC of indinavir, were not significantly affected by the simultaneous use of indinavir (800 mg 3 times a day) and voriconazole. Other HIV protease inhibitors (CYP3A4 inhibitors): In vitro studies have shown that voriconazole has an inhibitory effect on the metabolism of HIV protease inhibitors (such as saquinavir, amprenavir and nelfinavir), and protease inhibitors can also inhibit the metabolism of voriconazole. However, the results of in vitro studies alone cannot predict the situation in the human body after the two drugs are used together. Therefore, the efficacy and/or toxicity of the drugs must be monitored when these two drugs are used simultaneously. Non-nucleoside reverse transcriptase inhibitors (NNRTIs, CYP3A4 substrates, CYP3A4 inhibitors, or CYP450 inducers): In vitro studies have shown that delavirdine and efavirenz may inhibit voriconazole metabolism. Although not studied, efavirenz and nevirapine may induce voriconazole metabolism, and voriconazole may also inhibit NNRTI metabolism. Due to the lack of in vivo studies, the efficacy and/or toxicity of the drugs should be closely monitored when the two are used together.

The tablets should be sealed and stored at room temperature. The validity period is 3 years.

Chongqing Lummy LONG YU Pharmaceutical Co., Ltd.

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  2015-09-08

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