Vfend Tablets
Name: Vfend Tablets
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Indications and Usage for Vfend Tablets
VFEND is indicated for use in patients 12 years of age and older in the treatment of the following fungal infections:
Invasive Aspergillosis
In clinical trials, the majority of isolates recovered were Aspergillus fumigatus. There was a small number of cases of culture-proven disease due to species of Aspergillus other than A. fumigatus [see Clinical Studies (14.1) and Clinical Pharmacology (12.4)].
Candidemia in Non-neutropenic Patients and the Following Candida Infections: Disseminated Infections in Skin and Infections in Abdomen, Kidney, Bladder Wall, and Wounds
[see Clinical Studies (14.2) and Clinical Pharmacology (12.4)]
Esophageal Candidiasis
[see Clinical Studies (14.3) and Clinical Pharmacology (12.4)]
Serious Fungal Infections Caused by Scedosporium apiospermum (Asexual Form of Pseudallescheria boydii) and Fusarium spp. Including Fusarium solani, in Patients Intolerant of, or Refractory to, Other Therapy
[see Clinical Studies (14.4) and Clinical Pharmacology (12.4)]
Specimens for fungal culture and other relevant laboratory studies (including histopathology) should be obtained prior to therapy to isolate and identify causative organism(s). Therapy may be instituted before the results of the cultures and other laboratory studies are known. However, once these results become available, antifungal therapy should be adjusted accordingly.
Vfend Tablets Dosage and Administration
Instructions for Use in All Patients
Vfend Tablets or Oral Suspension should be taken at least one hour before or after a meal.
VFEND I.V. for Injection requires reconstitution to 10 mg/mL and subsequent dilution to 5 mg/mL or less prior to administration as an infusion, at a maximum rate of 3 mg/kg per hour over 1 to 2 hours.
Do not administer as an IV bolus injection.
Use of VFEND I.V. With Other Parenteral Drug Products
Blood products and concentrated electrolytes
VFEND I.V. must not be infused concomitantly with any blood product or short-term infusion of concentrated electrolytes, even if the two infusions are running in separate intravenous lines (or cannulas). Electrolyte disturbances such as hypokalemia, hypomagnesemia and hypocalcemia should be corrected prior to initiation of and during VFEND therapy [see Warnings and Precautions (5.8)].
Intravenous solutions containing (non-concentrated) electrolytes
VFEND I.V. can be infused at the same time as other intravenous solutions containing (non-concentrated) electrolytes, but must be infused through a separate line.
Total parenteral nutrition (TPN)
VFEND I.V. can be infused at the same time as total parenteral nutrition, but must be infused in a separate line. If infused through a multiple-lumen catheter, TPN needs to be administered using a different port from the one used for VFEND I.V.
Recommended Dosing in Adults
Invasive aspergillosis and serious fungal infections due to Fusarium spp. and Scedosporium apiospermum
See Table 1. Therapy must be initiated with the specified loading dose regimen of intravenous VFEND on Day 1 followed by the recommended maintenance dose (RMD) regimen. Intravenous treatment should be continued for at least 7 days. Once the patient has clinically improved and can tolerate medication given by mouth, the oral tablet form or oral suspension form of VFEND may be utilized. The recommended oral maintenance dose of 200 mg achieves a voriconazole exposure similar to 3 mg/kg IV; a 300 mg oral dose achieves an exposure similar to 4 mg/kg IV. Switching between the intravenous and oral formulations is appropriate because of the high bioavailability of the oral formulation in adults [see Clinical Pharmacology (12)].
Candidemia in non-neutropenic patients and other deep tissue Candida infections
See Table 1. Patients should be treated for at least 14 days following resolution of symptoms or following last positive culture, whichever is longer.
Esophageal Candidiasis
See Table 1. Patients should be treated for a minimum of 14 days and for at least 7 days following resolution of symptoms.
| Infection | Loading dose | Maintenance Dose*,† | |
|---|---|---|---|
| IV | IV | Oral‡ | |
| * Increase dose when VFEND is co-administered with phenytoin or efavirenz (7); Decrease dose in patients with hepatic impairment (2.7) † In healthy volunteer studies, the 200 mg oral q12h dose provided an exposure (AUCτ) similar to a 3 mg/kg IV q12h dose; the 300 mg oral q12h dose provided an exposure (AUCτ) similar to a 4 mg/kg IV q12h dose [see Clinical Pharmacology (12)]. ‡ Adult patients who weigh less than 40 kg should receive half of the oral maintenance dose. § In a clinical study of invasive aspergillosis, the median duration of IV VFEND therapy was 10 days (range 2–85 days). The median duration of oral VFEND therapy was 76 days (range 2–232 days) [see Clinical Studies (14.1)]. ¶ In clinical trials, patients with candidemia received 3 mg/kg IV q12h as primary therapy, while patients with other deep tissue Candida infections received 4 mg/kg q12h as salvage therapy. Appropriate dose should be based on the severity and nature of the infection. # Not evaluated in patients with esophageal candidiasis. | |||
| Invasive Aspergillosis§ | 6 mg/kg q12h for the first 24 hours | 4 mg/kg q12h | 200 mg q12h |
| Candidemia in nonneutropenic patients and other deep tissue Candida infections | 6 mg/kg q12h for the first 24 hours | 3–4 mg/kg q12h¶ | 200 mg q12h |
| Esophageal Candidiasis | # | # | 200 mg q12h |
| Scedosporiosis and Fusariosis | 6 mg/kg q12h for the first 24 hours | 4 mg/kg q12h | 200 mg q12h |
Dosage Adjustment
If patient response is inadequate, the oral maintenance dose may be increased from 200 mg every 12 hours (similar to 3 mg/kg IV q12h) to 300 mg every 12 hours (similar to 4 mg/kg IV q12h). For adult patients weighing less than 40 kg, the oral maintenance dose may be increased from 100 mg every 12 hours to 150 mg every 12 hours. If patient is unable to tolerate 300 mg orally every 12 hours, reduce the oral maintenance dose by 50 mg steps to a minimum of 200 mg every 12 hours (or to 100 mg every 12 hours for adult patients weighing less than 40 kg).
If patient is unable to tolerate 4 mg/kg IV q12h, reduce the intravenous maintenance dose to 3 mg/kg q12h.
The maintenance dose of voriconazole should be increased when co-administered with phenytoin or efavirenz [see Drug Interactions (7)].
The maintenance dose of voriconazole should be reduced in patients with mild to moderate hepatic impairment, Child-Pugh Class A and B [see Dosage and Administration (2.7)]. There are no PK data to allow for dosage adjustment recommendations in patients with severe hepatic impairment (Child-Pugh Class C).
Duration of therapy should be based on the severity of the patient's underlying disease, recovery from immunosuppression, and clinical response.
Intravenous Administration
Reconstitution
The powder is reconstituted with 19 mL of Water For Injection to obtain an extractable volume of 20 mL of clear concentrate containing 10 mg/mL of voriconazole. It is recommended that a standard 20 mL (non-automated) syringe be used to ensure that the exact amount (19.0 mL) of Water for Injection is dispensed. Discard the vial if a vacuum does not pull the diluent into the vial. Shake the vial until all the powder is dissolved.
Dilution
VFEND must be infused over 1–2 hours, at a concentration of 5 mg/mL or less. Therefore, the required volume of the 10 mg/mL VFEND concentrate should be further diluted as follows (appropriate diluents listed below):
- Calculate the volume of 10 mg/mL VFEND concentrate required based on the patient's weight (see Table 2).
- In order to allow the required volume of VFEND concentrate to be added, withdraw and discard at least an equal volume of diluent from the infusion bag or bottle to be used. The volume of diluent remaining in the bag or bottle should be such that when the 10 mg/mL VFEND concentrate is added, the final concentration is not less than 0.5 mg/mL nor greater than 5 mg/mL.
- Using a suitable size syringe and aseptic technique, withdraw the required volume of VFEND concentrate from the appropriate number of vials and add to the infusion bag or bottle. Discard Partially Used Vials.
The final VFEND solution must be infused over 1–2 hours at a maximum rate of 3 mg/kg per hour.
| Volume of VFEND Concentrate (10 mg/mL) required for: | |||
|---|---|---|---|
| Body Weight (kg) | 3 mg/kg dose (number of vials) | 4 mg/kg dose (number of vials) | 6 mg/kg dose (number of vials) |
| 30 | 9.0 mL (1) | 12 mL (1) | 18 mL (1) |
| 35 | 10.5 mL (1) | 14 mL (1) | 21 mL (2) |
| 40 | 12.0 mL (1) | 16 mL (1) | 24 mL (2) |
| 45 | 13.5 mL (1) | 18 mL (1) | 27 mL (2) |
| 50 | 15.0 mL (1) | 20 mL (1) | 30 mL (2) |
| 55 | 16.5 mL (1) | 22 mL (2) | 33 mL (2) |
| 60 | 18.0 mL (1) | 24 mL (2) | 36 mL (2) |
| 65 | 19.5 mL (1) | 26 mL (2) | 39 mL (2) |
| 70 | 21.0 mL (2) | 28 mL (2) | 42 mL (3) |
| 75 | 22.5 mL (2) | 30 mL (2) | 45 mL (3) |
| 80 | 24.0 mL (2) | 32 mL (2) | 48 mL (3) |
| 85 | 25.5 mL (2) | 34 mL (2) | 51 mL (3) |
| 90 | 27.0 mL (2) | 36 mL (2) | 54 mL (3) |
| 95 | 28.5 mL (2) | 38 mL (2) | 57 mL (3) |
| 100 | 30.0 mL (2) | 40 mL (2) | 60 mL (3) |
VFEND I.V. for Injection is a single dose unpreserved sterile lyophile. Therefore, from a microbiological point of view, once reconstituted, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and should not be longer than 24 hours at 2° to 8°C (36° to 46°F). This medicinal product is for single use only and any unused solution should be discarded. Only clear solutions without particles should be used.
The reconstituted solution can be diluted with:
9 mg/mL (0.9%) Sodium Chloride USP
Lactated Ringers USP
5% Dextrose and Lactated Ringers USP
5% Dextrose and 0.45% Sodium Chloride USP
5% Dextrose USP
5% Dextrose and 20 mEq Potassium Chloride USP
0.45% Sodium Chloride USP
5% Dextrose and 0.9% Sodium Chloride USP
The compatibility of VFEND I.V. with diluents other than those described above is unknown (see Incompatibilities below).
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Incompatibilities
VFEND I.V. must not be diluted with 4.2% Sodium Bicarbonate Infusion. The mildly alkaline nature of this diluent caused slight degradation of VFEND after 24 hours storage at room temperature. Although refrigerated storage is recommended following reconstitution, use of this diluent is not recommended as a precautionary measure. Compatibility with other concentrations is unknown.
Oral Suspension
Reconstitution
Tap the bottle to release the powder. Add 46 mL of water to the bottle. Shake the closed bottle vigorously for about 1 minute. Remove child-resistant cap and push bottle adaptor into the neck of the bottle. Replace the cap. Write the date of expiration of the reconstituted suspension on the bottle label (the shelf-life of the reconstituted suspension is 14 days at controlled room temperature 15–30°C [59–86°F]).
Instructions for use
Shake the closed bottle of reconstituted suspension for approximately 10 seconds before each use. The reconstituted oral suspension should only be administered using the oral dispenser supplied with each pack.
Incompatibilities
VFEND for Oral Suspension and the 40 mg/mL reconstituted oral suspension should not be mixed with any other medication or additional flavoring agent. It is not intended that the suspension be further diluted with water or other vehicles.
Use in Patients With Hepatic Impairment
In the clinical program, patients were included who had baseline liver function tests (ALT, AST) up to 5 times the upper limit of normal. No dose adjustment is necessary in patients with this degree of abnormal liver function, but continued monitoring of liver function tests for further elevations is recommended [see Warnings and Precautions (5.9)].
It is recommended that the standard loading dose regimens be used but that the maintenance dose be halved in patients with mild to moderate hepatic cirrhosis (Child-Pugh Class A and B) [see Clinical Pharmacology (12.3)].
VFEND has not been studied in patients with severe hepatic cirrhosis (Child-Pugh Class C) or in patients with chronic hepatitis B or chronic hepatitis C disease. VFEND has been associated with elevations in liver function tests and clinical signs of liver damage, such as jaundice, and should only be used in patients with severe hepatic impairment if the benefit outweighs the potential risk. Patients with hepatic impairment must be carefully monitored for drug toxicity.
Use in Patients With Renal Impairment
The pharmacokinetics of orally administered VFEND are not significantly affected by renal impairment. Therefore, no adjustment is necessary for oral dosing in patients with mild to severe renal impairment [see Clinical Pharmacology (12.3)].
In patients with moderate or severe renal impairment (creatinine clearance <50 mL/min), accumulation of the intravenous vehicle, SBECD, occurs. Oral voriconazole should be administered to these patients, unless an assessment of the benefit/risk to the patient justifies the use of intravenous voriconazole. Serum creatinine levels should be closely monitored in these patients, and, if increases occur, consideration should be given to changing to oral voriconazole therapy [see Warnings and Precautions (5.10)].
Voriconazole is hemodialyzed with clearance of 121 mL/min. The intravenous vehicle, SBECD, is hemodialyzed with clearance of 55 mL/min. A 4-hour hemodialysis session does not remove a sufficient amount of voriconazole to warrant dose adjustment.
Drug Interactions
| Drug/Drug Class (Mechanism of Interaction by the Drug) | Voriconazole Plasma Exposure (Cmax and AUCτ after 200 mg q12h) | Recommendations for Voriconazole Dosage Adjustment/Comments |
|---|---|---|
| * Results based on in vivo clinical studies generally following repeat oral dosing with 200 mg q12h voriconazole to healthy subjects † Results based on in vivo clinical study following repeat oral dosing with 400 mg q12h for 1 day, then 200 mg q12h for at least 2 days voriconazole to healthy subjects ‡ Non-Nucleoside Reverse Transcriptase Inhibitors | ||
| Rifampin* and Rifabutin* (CYP450 Induction) | Significantly Reduced | Contraindicated |
| Efavirenz (400 mg q24h)† (CYP450 Induction) | Significantly Reduced | Contraindicated |
| Efavirenz (300 mg q24h)† (CYP450 Induction) | Slight Decrease in AUCτ | When voriconazole is coadministered with efavirenz, voriconazole oral maintenance dose should be increased to 400 mg q12h and efavirenz should be decreased to 300 mg q24h |
| High-dose Ritonavir (400 mg q12h)† (CYP450 Induction) | Significantly Reduced | Contraindicated |
| Low-dose Ritonavir (100 mg q12h)† (CYP450 Induction) | Reduced | Coadministration of voriconazole and low-dose ritonavir (100 mg q12h) should be avoided, unless an assessment of the benefit/risk to the patient justifies the use of voriconazole |
| Carbamazepine (CYP450 Induction) | Not Studied In Vivo or In Vitro, but Likely to Result in Significant Reduction | Contraindicated |
| Long Acting Barbiturates (CYP450 Induction) | Not Studied In Vivo or In Vitro, but Likely to Result in Significant Reduction | Contraindicated |
| Phenytoin* (CYP450 Induction) | Significantly Reduced | Increase voriconazole maintenance dose from 4 mg/kg to 5 mg/kg IV q12h or from 200 mg to 400 mg orally q12h (100 mg to 200 mg orally q12h in patients weighing less than 40 kg) |
| St. John's Wort (CYP450 inducer; P-gp inducer) | Significantly Reduced | Contraindicated |
| Oral Contraceptives† containing ethinyl estradiol and norethindrone (CYP2C19 Inhibition) | Increased | Monitoring for adverse events and toxicity related to voriconazole is recommended when coadministered with oral contraceptives |
| Fluconazole† (CYP2C9, CYP2C19 and CYP3A4 Inhibition) | Significantly Increased | Avoid concomitant administration of voriconazole and fluconazole. Monitoring for adverse events and toxicity related to voriconazole is started within 24 h after the last dose of fluconazole. |
| Other HIV Protease Inhibitors (CYP3A4 Inhibition) | In Vivo Studies Showed No Significant Effects of Indinavir on Voriconazole Exposure | No dosage adjustment in the voriconazole dosage needed when coadministered with indinavir |
| In Vitro Studies Demonstrated Potential for Inhibition of Voriconazole Metabolism (Increased Plasma Exposure) | Frequent monitoring for adverse events and toxicity related to voriconazole when coadministered with other HIV protease inhibitors | |
| Other NNRTIs‡ (CYP3A4 Inhibition or CYP450 Induction) | In Vitro Studies Demonstrated Potential for Inhibition of Voriconazole Metabolism by Delavirdine and Other NNRTIs (Increased Plasma Exposure) | Frequent monitoring for adverse events and toxicity related to voriconazole |
| A Voriconazole-Efavirenz Drug Interaction Study Demonstrated the Potential for the Metabolism of Voriconazole to be Induced by Efavirenz and Other NNRTIs (Decreased Plasma Exposure) | Careful assessment of voriconazole effectiveness | |
| Drug/Drug Class (Mechanism of Interaction by Voriconazole) | Drug Plasma Exposure (Cmax and AUCτ) | Recommendations for Drug Dosage Adjustment/Comments |
|---|---|---|
| * Results based on in vivo clinical studies generally following repeat oral dosing with 200 mg BID voriconazole to healthy subjects † Results based on in vivo clinical study following repeat oral dosing with 400 mg q12h for 1 day, then 200 mg q12h for at least 2 days voriconazole to healthy subjects ‡ Results based on in vivo clinical study following repeat oral dosing with 400 mg q12h for 1 day, then 200 mg q12h for 4 days voriconazole to subjects receiving a methadone maintenance dose (30–100 mg q24h) § Non-Steroidal Anti-Inflammatory Drug ¶ Non-Nucleoside Reverse Transcriptase Inhibitors | ||
| Sirolimus* (CYP3A4 Inhibition) | Significantly Increased | Contraindicated |
| Rifabutin* (CYP3A4 Inhibition) | Significantly Increased | Contraindicated |
| Efavirenz (400 mg q24h)† (CYP3A4 Inhibition) | Significantly Increased | Contraindicated |
| Efavirenz (300 mg q24h)† (CYP3A4 Inhibition) | Slight Increase in AUCτ | When voriconazole is coadministered with efavirenz, voriconazole oral maintenance dose should be increased to 400 mg q12h and efavirenz should be decreased to 300 mg q24h |
| High-dose Ritonavir (400 mg q12h)†(CYP3A4 Inhibition) | No Significant Effect of Voriconazole on Ritonavir Cmax or AUCτ | Contraindicated because of significant reduction of voriconazole Cmax and AUCτ |
| Low-dose Ritonavir (100 mg q12h)† | Slight Decrease in Ritonavir Cmax and AUCτ | Coadministration of voriconazole and low-dose ritonavir (100 mg q12h) should be avoided (due to the reduction in voriconazole Cmax and AUCτ) unless an assessment of the benefit/risk to the patient justifies the use of voriconazole |
| Terfenadine, Astemizole, Cisapride, Pimozide, Quinidine (CYP3A4 Inhibition) | Not Studied In Vivo or In Vitro, but Drug Plasma Exposure Likely to be Increased | Contraindicated because of potential for QT prolongation and rare occurrence of torsade de pointes |
| Ergot Alkaloids (CYP450 Inhibition) | Not Studied In Vivo or In Vitro, but Drug Plasma Exposure Likely to be Increased | Contraindicated |
| Cyclosporine* (CYP3A4 Inhibition) | AUCτ Significantly Increased; No Significant Effect on Cmax | When initiating therapy with VFEND in patients already receiving cyclosporine, reduce the cyclosporine dose to one-half of the starting dose and follow with frequent monitoring of cyclosporine blood levels. Increased cyclosporine levels have been associated with nephrotoxicity. When VFEND is discontinued, cyclosporine concentrations must be frequently monitored and the dose increased as necessary. |
| Methadone‡ (CYP3A4 Inhibition) | Increased | Increased plasma concentrations of methadone have been associated with toxicity including QT prolongation. Frequent monitoring for adverse events and toxicity related to methadone is recommended during coadministration. Dose reduction of methadone may be needed |
| Fentanyl (CYP3A4 Inhibition) | Increased | Reduction in the dose of fentanyl and other long-acting opiates metabolized by CYP3A4 should be considered when coadministered with VFEND. Extended and frequent monitoring for opiate-associated adverse events may be necessary [see Drug Interactions (7)] |
| Alfentanil (CYP3A4 Inhibition) | Significantly Increased | Reduction in the dose of alfentanil and other opiates metabolized by CYP3A4 (e.g., sufentanil) should be considered when coadministered with VFEND. A longer period for monitoring respiratory and other opiate-associated adverse events may be necessary [see Drug Interactions (7)]. |
| Oxycodone (CYP3A4 Inhibition) | Significantly Increased | Reduction in the dose of oxycodone and other long-acting opiates metabolized by CYP3A4 should be considered when coadministered with VFEND. Extended and frequent monitoring for opiate-associated adverse events may be necessary [see Drug Interactions (7)]. |
| NSAIDs§ including. ibuprofen and diclofenac | Increased | Frequent monitoring for adverse events and toxicity related to NSAIDs. Dose reduction of NSAIDs may be needed [see Drug Interactions (7)]. |
| (CYP2C9 Inhibition) | ||
| Tacrolimus* (CYP3A4 Inhibition) | Significantly Increased | When initiating therapy with VFEND in patients already receiving tacrolimus, reduce the tacrolimus dose to one-third of the starting dose and follow with frequent monitoring of tacrolimus blood levels. Increased tacrolimus levels have been associated with nephrotoxicity. When VFEND is discontinued, tacrolimus concentrations must be frequently monitored and the dose increased as necessary. |
| Phenytoin* (CYP2C9 Inhibition) | Significantly Increased | Frequent monitoring of phenytoin plasma concentrations and frequent monitoring of adverse effects related to phenytoin. |
| Oral Contraceptives containing ethinyl estradiol and norethindrone (CYP3A4 Inhibition)† | Increased | Monitoring for adverse events related to oral contraceptives is recommended during coadministration. |
| Warfarin* (CYP2C9 Inhibition) | Prothrombin Time Significantly Increased | Monitor PT or other suitable anti-coagulation tests. Adjustment of warfarin dosage may be needed. |
| Omeprazole* (CYP2C19/3A4 Inhibition) | Significantly Increased | When initiating therapy with VFEND in patients already receiving omeprazole doses of 40 mg or greater, reduce the omeprazole dose by one-half. The metabolism of other proton pump inhibitors that are CYP2C19 substrates may also be inhibited by voriconazole and may result in increased plasma concentrations of other proton pump inhibitors. |
| Other HIV Protease Inhibitors (CYP3A4 Inhibition) | In Vivo Studies Showed No Significant Effects on Indinavir Exposure | No dosage adjustment for indinavir when coadministered with VFEND |
| In Vitro Studies Demonstrated Potential for Voriconazole to Inhibit Metabolism (Increased Plasma Exposure) | Frequent monitoring for adverse events and toxicity related to other HIV protease inhibitors | |
| Other NNRTIs¶ (CYP3A4 Inhibition) | A Voriconazole-Efavirenz Drug Interaction Study Demonstrated the Potential for Voriconazole to Inhibit Metabolism of Other NNRTIs (Increased Plasma Exposure) | Frequent monitoring for adverse events and toxicity related to NNRTI |
| Benzodiazepines (CYP3A4 Inhibition) | In Vitro Studies Demonstrated Potential for Voriconazole to Inhibit Metabolism (Increased Plasma Exposure) | Frequent monitoring for adverse events and toxicity (i.e., prolonged sedation) related to benzodiazepines metabolized by CYP3A4 (e.g., midazolam, triazolam, alprazolam). Adjustment of benzodiazepine dosage may be needed. |
| HMG-CoA Reductase Inhibitors (Statins) (CYP3A4 Inhibition) | In Vitro Studies Demonstrated Potential for Voriconazole to Inhibit Metabolism (Increased Plasma Exposure) | Frequent monitoring for adverse events and toxicity related to statins. Increased statin concentrations in plasma have been associated with rhabdomyolysis. Adjustment of the statin dosage may be needed. |
| Dihydropyridine Calcium Channel Blockers (CYP3A4 Inhibition) | In Vitro Studies Demonstrated Potential for Voriconazole to Inhibit Metabolism (Increased Plasma Exposure) | Frequent monitoring for adverse events and toxicity related to calcium channel blockers. Adjustment of calcium channel blocker dosage may be needed. |
| Sulfonylurea Oral Hypoglycemics (CYP2C9 Inhibition) | Not Studied In Vivo or In Vitro, but Drug Plasma Exposure Likely to be Increased | Frequent monitoring of blood glucose and for signs and symptoms of hypoglycemia. Adjustment of oral hypoglycemic drug dosage may be needed. |
| Vinca Alkaloids (CYP3A4 Inhibition) | Not Studied In Vivo or In Vitro, but Drug Plasma Exposure Likely to be Increased | Frequent monitoring for adverse events and toxicity (i.e., neurotoxicity) related to vinca alkaloids. Reserve azole antifungals, including voriconazole, for patients receiving a vinca alkaloid who have no alternative antifungal treatment options. |
| Everolimus (CYP3A4 Inhibition) | Not Studied In Vivo or In Vitro, but Drug Plasma Exposure Likely to be Increased | Concomitant administration of voriconazole and everolimus is not recommended. |
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment of Fertility
Two-year carcinogenicity studies were conducted in rats and mice. Rats were given oral doses of 6, 18 or 50 mg/kg voriconazole, or 0.2, 0.6, or 1.6 times the recommended maintenance dose on a mg/m2 basis. Hepatocellular adenomas were detected in females at 50 mg/kg and hepatocellular carcinomas were found in males at 6 and 50 mg/kg. Mice were given oral doses of 10, 30 or 100 mg/kg voriconazole, or 0.1, 0.4, or 1.4 times the RMD on a mg/m2 basis. In mice, hepatocellular adenomas were detected in males and females and hepatocellular carcinomas were detected in males at 1.4 times the RMD of voriconazole.
Voriconazole demonstrated clastogenic activity (mostly chromosome breaks) in human lymphocyte cultures in vitro. Voriconazole was not genotoxic in the Ames assay, CHO HGPRT assay, the mouse micronucleus assay or the in vivo DNA repair test (Unscheduled DNA Synthesis assay).
Voriconazole administration induced no impairment of male or female fertility in rats dosed at 50 mg/kg, or 1.6 times the RMD (recommended maintenance dose).
PRINCIPAL DISPLAY PANEL - 50 mg Tablet Bottle Label
Pfizer
NDC 0049-3170-30
Vfend®
(voriconazole)
50 mg
Tablets
30 Tablets
Rx only
PRINCIPAL DISPLAY PANEL - 200 mg Vial Label
NDC 0049-3190-28
Vfend® I.V.
(voriconazole) for injection
200 mg*
200 mg* of voriconazole
No Latex
No Preservatives
Sterile Single Use Vial
For I.V. Infusion Only
Pfizer Injectables
Rx only