Anticytomegalovirus Agents

Anticytomegalovirus Agents is a topic covered in the Washington Manual of Medical Therapeutics.

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  • Ganciclovir (5 mg/kg IV q12h for 14–21 days for induction therapy of cytomegalovirus [CMV] retinitis, followed by 6 mg/kg IV for 5 days every week or 5 mg/kg IV q24h) is used to treat CMV infections.
    • It has activity against HSV and VZV, but safer drugs are available to treat those infections. The drug is widely distributed in the body, including the CSF.
    • It is indicated for treatment of CMV retinitis and other serious CMV infections in immunocompromised patients (e.g., transplant and AIDS patients). Chronic maintenance therapy is required to suppress CMV disease in patients with AIDS until CD4 count is >200 cell/µL.
    • Adverse events: Neutropenia is the main therapy-limiting adverse effect and may require treatment with granulocyte colony-stimulating factor for management (300 μg SC daily to weekly). Thrombocytopenia, rash, confusion, headache, nephrotoxicity, and GI disturbances may also occur. Blood counts and electrolytes should be monitored weekly while the patient is receiving therapy. Concomitant use of other agents with nephrotoxic or bone marrow suppressive effects should be avoided, if possible.
  • Valganciclovir (900 mg PO q12–24h) is the oral prodrug of ganciclovir. This agent has substantial bioavailability and can be used for treatment of CMV retinitis. Adverse events are the same as those for ganciclovir.
  • Foscarnet (60 mg/kg IV q8h or 90 mg/kg IV q12h for 14–21 days as induction therapy, followed by 90–120 mg/kg IV q24h as maintenance therapy for CMV; 40 mg/kg IV q8h for acyclovir-resistant HSV and VZV) is used to treat acyclovir-resistant HSV/VZV infections and ganciclovir-resistant CMV infections. It can be used in patients who are not tolerating or not responding to ganciclovir.

    Adverse events: Nephrotoxicity is a major concern. CrCl should be determined at baseline, and electrolytes (PO4, Ca2+, Mg2+, and K+) and serum creatinine should be checked at least twice a week. Normal saline (500–1000 mL) should be given before and during infusions to minimize nephrotoxicity. Foscarnet should be avoided in patients with a serum creatinine of >2.8 mg/dL or baseline CrCl of <50 mL/min. Concomitant use of other nephrotoxins should be avoided. Foscarnet chelates divalent cations can cause tetany even with normal serum calcium levels. Use of foscarnet with pentamidine can cause severe hypocalcemia. Other side effects include seizures, phlebitis, rash, and genital ulcers. Prolonged therapy with foscarnet should be monitored by physicians who are experienced with administration of home IV therapy and can systematically monitor patients’ laboratory results.

  • Cidofovir (5 mg/kg IV q wk for 2 weeks as induction therapy, followed by 5 mg/kg IV q14d chronically as maintenance therapy) is used primarily to treat CMV retinitis in patients with AIDS who are not responding to ganciclovir or foscarnet. It can be administered through a peripheral IV line.
    • Adverse events: The most common adverse event is nephrotoxicity. It should be avoided in patients with a CrCl of <55 mL/min, a serum creatinine >1.5 mg/dL, significant proteinuria, or a recent history of receipt of other nephrotoxic medications.
    • Each cidofovir dose should be administered with probenecid (2 g PO 3 hours before the infusion and then 1 g at 2 and 8 hours after the infusion) along with 1 L normal saline IV 1–2 hours before the infusion to minimize nephrotoxicity. Patients should have a serum creatinine and urine protein check before each dose of cidofovir is given. This drug requires systematic monitoring of laboratory studies and close physician follow-up.
  • Letermovir (480 mg IV or PO q24h) is a CMV DNA terminase inhibitor that is FDA approved for CMV prophylaxis in allogeneic hematopoietic stem cell transplant through 100 days posttransplant. It has been anecdotally utilized for treatment of CMV infection, although this is not an established indication. Letermovir is contraindicated with pimozide and ergot alkaloids. Concomitant use of cyclosporine mandates dose reduction of letermovir to 240 mg q24h. The drug appears to be well-tolerated.

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