Voriconazole is an active substance that medical professionals can use to treat fungal infections. It thus belongs to the group of antifungal drugs. The effect of the drug is based on a substance that damages the cell wall of the fungus. Possible areas of application include infections with Aspergillus, Fusarium, Scedosporium and Candida, although physicians must take into account the numerous potential interactions.
What is voriconazole?
Voriconazole is an active ingredient that healthcare professionals can use to treat fungal infections. Possible uses include infections with Aspergillus. Voriconazole is an active pharmaceutical ingredient with the molecular formula C16H14F3N5O. The drug belongs to the group of antifungal drugs as it can be used to treat fungal infections originating from the pathogens Aspergillus, Fusarium, Scedosporiu or Candida. In addition to the general indication, the use of the drug also depends on individual factors. Patients can take voriconazole either as an infusion or orally (usually as film-coated tablets), depending on the prescribed preparation. Solutions in liquid, for example for infusions and suspensions, must usually first be mixed from a white powder. Among other things, voriconazole can be better stored in this form. It is commercially available under the name Vfend, for example, as well as corresponding generics.
Pharmacological effect
Voriconazole acts against severe fungal infections by inhibiting the fungus in the construction of its cell walls. The cells of a fungus, like plant cells, have both a cell wall and a cell membrane. Among other things, the cell wall gives them stability and has a protective function. Unlike plants and fungi, humans do not have cell walls around their cells, but only a membrane. To prevent the fungus from building its cell walls, voriconazole interferes with the pathogen’s metabolism and disrupts the enzyme lanosterol 14α-demethylase. This enzyme also exists in organisms other than fungi and is involved in the synthesis of various biological molecules. These include certain lipids, vitamins, and steroids; one of these steroids that certain fungi require is ergosterol. Lanosterol-14α-demethylase plays an important role in the conversion of the parent compound ianosterol into ergosterol, which, among other things, determines the hardness of the membrane and thereby influences cell wall construction.
Medical application and use
Physicians prescribe voriconazole primarily for severe fungal infections, for example, when organ systems are at risk or treatment attempts with other drugs have been unsuccessful. Indications include severe infections with Aspergillus, Candida, Fusarium and Scedosporium. Aspergillus spores are found in large numbers in the air; a healthy person usually inhales and exhales them without causing infection in the body. However, drugs that inhibit the immune system (immunosuppressants) in particular can cause spores that are in themselves relatively harmless, such as those of Aspergillus, to lead to serious infections. In many cases, one of the many subspecies of the fungus attacks the lungs first, settling in the tissue and forming a watering-can-like neck, to which the fungus also owes the name “watering-can mold.” Aspergillus fumigatus occurs particularly frequently as the causative agent of such aspergillosis. In the worst case, the fungal infection can lead to the destruction of tissue and the spread of the fungus throughout the organism. Therefore, the most effective treatment is essential. Aspergillosis can also affect the central nervous system, which was a major problem before voriconazole was approved – because not every drug can reach the brain and spinal cord and thus combat Aspergillus spread. Voriconazole therefore represented a significant milestone in the treatment of central nervous system aspergillosis. Another example of use for voriconazole is persistent Candida infections (thrush) that have not been successfully treated with other agents. Candida, too, does not normally pose a significant threat to the human organism and lives in or on the human body in a balanced equilibrium with other microorganisms.Disturbances in this balance can result in the spread of Candida: opportunistic infection occurs, often affecting several parts of the body simultaneously.
Risks and side effects
Common side effects of voriconazole include digestive symptoms such as abdominal pain, vomiting, nausea, and diarrhea, as well as fever, rash, and peripheral edema. Peripheral edema is water retention, for example in the legs, which manifests as swelling of the affected tissue. Neurological and psychiatric symptoms may also manifest as a result of the medication; these include headaches, visual disturbances, drowsiness and sleepiness, as well as psychotic symptoms such as hallucinations, confusion, anxiety and depression. In some cases, voriconazole proves toxic to the patient’s liver – medicine therefore also refers to hepatotoxicity in this context. Another possible side effect can be seen in the electrocardiogram (ECG), when the QT interval is prolonged, which marks the depolarization and repolarization of the heart chambers and lies between two characteristic sections of the ECG waves: between the QRS complex and the T wave. In addition, voriconazole may interact with numerous other drugs, including anticoagulants, astemizole, barbiturates, benzodiazepines, calcium antagonists, carbamazepine, ciclosporin, cisapride, preparations containing St. John’s wort, phenytoin, rifabutin, rifampicin, sirolimus, tacrolimus, and terfenadine.
