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Vfend (voriconazole)


Vfend (voriconazole) is a broad-spectrum triazole antimycotic indicated for the treatment of invasive aspergillosis, fluconazole-resistant serious invasive Candida infections and serious fungal infections caused by Scedosporium and Fusarium spp.


Vfend may be administered intravenously or orally, and it demonstrates a superior treatment response compared with conventional amphotericin B in the treatment of aspergillosis. This seems to be due to a wider therapeutic window; the adverse drug reaction   profile of voriconazole is apparently less severe than that of conventional amphotericin B.


The cost of Vfend is approximately the same as that of lipid-based formulations of amphotericin B, but substantially more than conventional amphotericin B, a therapy which, however, is often not feasible due to toxicity, especially renal toxicity. Voriconazole therapy for these rare conditions seems to be justified by the significantly improved response in patients with aspergillosis, the two different forms of administration available and the fact that voriconazole is otherwise used for conditions for which there is no other treatment at present.



Vfend was marketed on 16 September 2002.

Invasive fungal infection is a major cause of morbidity and mortality among immunocompromised patients. This can be attributed to the increase in use of broad-spectrum antibiotics and aggressive chemotherapeutic regimes and immunosuppressive therapies. HIV/AIDS and organ and bone marrow transplants are also contributory factors. Such infections are often caused by Candida and Aspergillus spp.


Vfend (voriconazole) is a broad-spectrum triazole antimycotic indicated for the treatment of invasive aspergillosis, fluconazole-resistant serious invasive Candida infections and serious fungal infections caused by Scedosporium and Fusarium spp.



Voriconazole proved more efficacious in the treatment of invasive aspergillosis than conventional amphotericin B with respect to both global response (53% vs. 31%) and survival at 12 weeks (71% vs. 58%) in a randomised, unblinded study of 277 patients.

Post hoc analysis of a population of 55 patients with a fluconazole-resistant Candida infection (no response after five days of treatment) out of the total population of 1493 patients in clinical studies with voriconazole, showed a positive response on  24 patients (44%), particularly  in the case of non-albicans species.

Finally, voriconazole seemed to be efficacious against Scedosporium spp. (19 responded out of 38 treated) and against Fusarium spp. (9 out of 21 treated), including a few cases with  involvement of the brain. These very rare patients, for whom no other treatment is available, were also  part of the total population of patients treated with voriconazole.

Adverse Drug Reactions

The adverse effects evaluation is based on data gathered from studies, most of which were open. The population comprised 1493 patients in clinical trials, of whom 561 received therapy for more than 12 weeks and 136 for more than six months.


Of severe side effects, hepato- and nephrotoxicity were observed, but nephrotoxicity was considerably rarer than in patients treated with conventional amphotericin B. Liver and kidney parameters must be monitored in patients. Accumulation of the intravenous vehicle SBECD occurs in patients with moderate to severe renal impairment; thus oral voriconazole should be used for these patients.


The most frequently reported adverse drug reaction during voriconazole therapy was visual disturbances (30%); they were most often characterised as mild and described as altered/enhanced perception, blurred vision, changed colour vision or photophobia. These visual disturbances are transient and reversible within about 60 minutes. Patients should not drive motor vehicles while this effect lasts.


Also observed were dermatological reactions of mild to moderate severity and photosensitivity. Skin rashes must be monitored. Experience with paediatric patients is limited.


Drug interactions

A number of known and potential interactions have been described for voriconazole, which is metabolised by – and inhibits – the cytochrome P450 isoenzymes CYP2C19, CYP2C9 and CYP3A4. Co-administration of terfenadine, cisapride, pimozide, quinidine, rifampicin, carbamazepine, phenobarbital, ergot alkaloids and sirolimus is contraindicated, and co-administration of phenytoin and rifabutin should be avoided.


Oral voriconazole must be administered at least one hour before or one hour following a meal due to interaction with high-fat meals.



The cost of maintenance therapy per day for an aspergillosis patient weighing 70 kg is as follows. Voriconazole costs

  • DKK 3120 (intravenous Vfend; 8 mg/kg/day)
  • DKK 601 (peroral Vfend; 400 mg/kg/day) Conventional amphotericin B costs
  • DKK 262 (Fungizone; 1 mg/kg/day)  By comparison, lipid formulations of amphotericin B cost
  • DKK 7625 (Ambisome; 3 mg/kg/day)
  • DKK 3880 (Abelcet; 5 mg/kg/day) 

Finally, Caspofungin (DKK 3591 for 50 mg/day) is registered for the treatment of aspergillosis patients who are refractory to or intolerant of amphotericin B therapy. These therapies are all for intravenous administration.


The cost of voriconazole  is higher than conventional amphotericin B treatment, which is, however, substantially more toxic.


Intravenous voriconazole costs about the same as amphotericin B lipid formulations, but the oral formulation is substantially less expensive.

Last modified: September 16th 2002

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