Voriconazole; Uses, Dosage, Side Effects, Interactions

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Voriconazole is a synthetic triazole with antifungal activity. Voriconazole selectively inhibits 14-alpha-lanosterol demethylation in fungi, preventing the production of ergosterol, an essential constituent of the fungal cell membrane, and resulting in fungal cell lysis

This includes aspergillosis, candidiasis, coccidioidomycosis, histoplasmosis, penicilliosis, and infections by Scedosporium or Fusarium. It can be taken by mouth or used by injection into a vein. It is used to treat invasive fungal infections that are generally seen in patients who are immunocompromised. These include invasive candidiasis, invasive aspergillosis, and emerging fungal infections. Voriconazole was approved for medical use in the United States in 2002.It is on the World Health Organization’s List of Essential Medicines, the most effective and safe medicines needed in a health system.

Mechanism of Action of Voriconazole

Voriconazole binds and inhibits ergosterol synthesis by inhibiting CYP450-dependent 14-alpha sterol demethylase. The inhibition of 14-alpha sterol demethylase results in a depletion of ergosterol in the fungal cell membrane. Fungal plasma membranes are similar to mammalian plasma membranes, differing in having the nonpolar sterol ergosterol, rather than cholesterol, as the principal sterol. Membrane sterols such as ergosterol provide structure, modulation of membrane fluidity, and possibly control of some physiologic events. Voriconazole effects the formation of the fungal plasma membrane by indirectly inhibiting the biosynthesis of ergosterol. This results in plasma membrane permeability changes and inhibition of growth.

Indications of Voriconazole

  • Candidemia
  • Blastomycosis
  • Coccidioidomycosis, Meningitis
  • Cutaneous Fungal Infection
  • Esophageal Candidiasis
  • Eumycetoma
  • Fungal Infection, Internal and Disseminated
  • Fungal Meningitis
  • Fungal Pneumonia
  • Fusariosis
  • Ocular Fungal Infection
  • Pseudoallescheriosis
  • Systemic Fungal Infection
  • Coccidioidomycosis
  • Esophageal Candidiasis
  • Fungal meningitis caused by Exserohilum Infection
  • Infections, Fungal
  • Invasive Aspergillosis
  • Penicillium marneffei infection
  • Disseminated Candidiasis
  • Non-neutropenic Candidemia
  • Refractory Fungal Infections
  • Voriconazole, is a broad spectrum, triazole antifungal agent and is indicated in adults and children aged 2 years and above as follows:
  • Treatment of invasive aspergillosis.
  • Treatment of candidemia in non-neutropenic patients.
  • Treatment of fluconazole-resistant serious invasive Candida infections (including C. krusei).
  • Treatment of serious fungal infections caused by Scedosporium spp. and Fusarium spp.
  • Voriconazole Accord should be administered primarily to patients with progressive, possibly life-threatening infections.
  • Prophylaxis of invasive fungal infections in high risk allogeneic hematopoietic stem cell transplant (HSCT) recipients.

Contra-Indications of Voriconazole

  • Low amount of magnesium in the blood
  • Low amount of calcium in the blood
  • Low amount of potassium in the blood
  • Sudden Blindness and Pain Upon Moving the Eye
  • Disease of the Muscle of the Heart with Enlargement
  • Very Rapid Heartbeat – Torsades de Pointes
  • Prolonged QT interval on EKG
  • Abnormal EKG with QT changes from Birth
  • Hardening of the Liver
  • Acute Inflammation of the Pancreas
  • Abnormal liver function tests
  • Pregnancy
  • A mother who is producing milk and breastfeeding
  • CYP2C19 poor metabolizer
  • Fluoride Deposits in Bone
  • Bone Inflammation with Pain
  • Allergies to Voriconazole & Antifungal – Triazole

Drug  Interactions of Voriconazole

  • Being metabolized by hepatic cytochrome P450, voriconazole interacts with many drugs.
  • Voriconazole should not be used in conjunction with many drugs including sirolimus, rifampicin, rifabutin, carbamazepine, quinidine and ergot alkaloids) and dose adjustments and/or monitoring when coadministered with others (including fluconazole, warfarin, cyclosporin, tacrolimus, omeprazole, and phenytoin).
  • Voriconazole may be safely administered with cimetidine, ranitidine, indinavir, macrolide antibiotics, mycophenolate, digoxin, and prednisolone

References

 

Voriconazole

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