News Articles on Voriconazole
Brand Names/Synonyms:
alosetron HCl is also known by the following brand names and/or synonymsDRG-0301; VCZ; VFEND; Vfend; Voriconazole; Voriconazole [Usan:Ban:Inn]
Drug Category:
alosetron HCl is categorized under the following by the FDA: Antifungals; ATC:J02AC03
Dosage Forms:
TABLET; Oral suspension; IV Injection
Absorption:
96%
Interactions:
-->Interactions for Voriconazole:
Tables 9 and 10 provide a summary of significant drug interactions with voriconazole that either have been studied
in vivo (clinically) or that may be expected to occur based on results of in vitro metabolism studies
with human liver microsomes. For more details, see CLINICAL PHARMACOLOGY - Drug
Interactions.
Table 9
Effect of Other Drugs on Voriconazole Pharmacokinetics
|
Drug/Drug Class (Mechanism of Interaction by the Drug)
|
Voriconazole Plasma Exposure (Cmax and AUCt after 200 mg Q12h)
|
Recommendations for Voriconazole Dosage Adjustment/Comments
|
|
Rifampin*, Efavirenz** and Rifabutin*(CYP450 Induction)
|
Significantly Reduced
|
Contraindicated
|
|
Ritonavir (400mg Q12h HIV ProteaseInhibitor)** (CYP450 Induction)
|
Significantly Reduced
|
Contraindicated
The effect of ritonavir (100 mg Q12h asused to inhibit CYP3A and increaseconcentrations of other
antiretroviraldrugs) on voriconazole concentrationshas not been studied.
|
|
Carbamazepine(CYP450 Induction)
|
Not Studied In Vivo or In Vitro, but Likelyto Result in Significant Reduction
|
Contraindicated
|
|
Long Acting Barbiturates(CYP450 Induction)
|
Not Studied In Vivo or In Vitro, but Likelyto Result in Significant Reduction
|
Contraindicated
|
|
Phenytoin*(CYP450 Induction)
|
Significantly Reduced
|
Increase voriconazole maintenance dosefrom 4 mg/kg to 5 mg/kg IV every 12hrs or from 200 mg to 400 mg
orallyevery 12 hrs (100 mg to 200 mg orallyevery 12 hrs in patients weighing lessthan 40 kg)
|
|
Other HIV Protease Inhibitors(CYP3A4 Inhibition)
|
In Vivo Studies Showed No SignificantEffects of Indinavir on VoriconazoleExposure
|
No dosage adjustment in thevoriconazole dosage needed whencoadministered with indinavir
|
|
In Vitro Studies Demonstrated Potential forInhibition of Voriconazole Metabolism(Increased Plasma Exposure)
|
Frequent monitoring for adverse eventsand toxicity related to voriconazolewhen coadministered with other
HIVprotease inhibitors
|
|
Other NNRTIs***(CYP3A4 Inhibition or CYP450Induction)
|
In Vitro Studies Demonstrated Potential forInhibition of Voriconazole Metabolism byDelavirdine and Other
NNRTIs (IncreasedPlasma Exposure)
|
Frequent monitoring for adverse eventsand toxicity related to voriconazole
|
|
A Voriconazole-Efavirenz Drug InteractionStudy Demonstrated the Potential for theMetabolism of Voriconazole
to be Inducedby Efavirenz and Other NNRTIs(Decreased Plasma Exposure)
|
Careful assessment of voriconazoleeffectiveness
|
*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 8 days voriconazole to healthy subjects
*** Non-Nucleoside Reverse Transcriptase Inhibitors
Table 10
Effect of Voriconazole on Pharmacokinetics of Other Drugs
|
Drug/Drug Class
(Mechanism of Interaction by
Voriconazole)
|
Drug Plasma Exposure
(Cmax and AUCt )
|
Recommendations for Drug Dosage
Adjustment/Comments
|
|
Sirolimus* (CYP3A4 Inhibition)
|
Significantly Increased
|
Contraindicated
|
|
Rifabutin* and Efavirenz** (CYP3A4 Inhibition)
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Significantly Increased
|
Contraindicated
|
|
Ritonavir (400 mg Q12h HIV Protease Inhibitor)**(CYP3A4 Inhibition)
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No significant effect of voriconazole on ritonavir Cmax or AUCt
|
Contraindicated because of significant reduction of voriconazole Cmax and AUCt
|
|
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)
|
AUCt 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
|
|
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.
|
|
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 Demonstrate 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 Demonstrates 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 Demonstrate 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 Demonstrate 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 Demonstrate 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. Adjustment of vinca
alkaloid dosage may be needed.
|
*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 8 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 QD)
**** Non-Nucleoside Reverse Transcriptase Inhibitors
Patients with Hepatic Insufficiency
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) receiving VFEND.
VFEND has not been studied in patients with severe cirrhosis (Child-Pugh Class C). 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 insufficiency if the benefit outweighs the potential risk. Patients with hepatic
insufficiency must be carefully monitored for drug toxicity.
Patients with Renal Insufficiency
In patients with moderate to severe renal dysfunction (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.
Renal Adverse Events
Acute renal failure has been observed in severely ill patients undergoing treatment with VFEND. Patients being
treated with voriconazole are likely to be treated concomitantly with nephrotoxic medications and have concurrent
conditions that may result in decreased renal function.
Monitoring of Renal Function
Patients should be monitored for the development of abnormal renal function. This should include laboratory
evaluation, particularly serum creatinine.
Dermatological Reactions
Patients have rarely developed serious cutaneous reactions, such as Stevens-Johnson syndrome, during treatment
with VFEND. If patients develop a rash, they should be monitored closely and consideration given to discontinuation
of VFEND. VFEND has been infrequently associated with photosensitivity skin reaction, especially during long-term
therapy. It is recommended that patients avoid strong, direct sunlight during VFEND therapy.
Chemical IUPAC Name:
2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol
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