Treatment

• Ganciclovir (5 mg/kg IV q12h for 14–21 d for induction therapy, followed by 5 mg/kg IV q24h) is a nucleoside analogue that inhibits DNA synthesis in the same manner as acyclovir. It has activity against HSV and VZV but is reserved for the treatment of CMV infections given its toxicity profile. Ganciclovir 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).
  • 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. A CBC and basic metabolic profile 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 and other systemic CMV infections. A 900 mg oral dose of valganciclovir is equivalent to 5 mg/kg of IV ganciclovir. Adverse events are the same as those for ganciclovir.
• Foscarnet (60 mg/kg IV q8h or 90 mg/kg IV q12h for 14–21 d 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 the major dose-limiting toxicity. CrCl, electrolytes (PO₄, Ca²⁺, Mg²⁺, and K⁺), and serum creatinine should be checked at baseline and at least twice weekly while on therapy. 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 and 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 wk as induction therapy, followed by 5 mg/kg IV q14d chronically as maintenance therapy) is used primarily to treat systemic CMV infections in patients who are not responding to ganciclovir or foscarnet.
  • Adverse events: The most common adverse event is nephrotoxicity. Cidofovir 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 h before the infusion and then 1 g at 2 and 8 h after the infusion) along with 1 L normal saline IV 1–2 h before the infusion to minimize nephrotoxicity. Patients should have a serum creatinine and urine protein checked 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. Significant drug interactions exist and should be determined prior to starting therapy. Letermovir is contraindicated with pimozide and ergot alkaloids. Concomitant use of cyclosporine mandates dose reduction of letermovir to 240 mg q24h.
  • Adverse events are rare but include GI upset, headache, and peripheral edema.