What is the recommended treatment for a patient with Cytomegalovirus (CMV) infection, particularly with valganciclovir (Valcyte)?

Valganciclovir Treatment for CMV Infection

Valganciclovir 900 mg orally twice daily for 14-21 days (induction), followed by 900 mg once daily (maintenance) is the recommended first-line treatment for CMV infection in most immunocompromised patients, with the drug taken with food to optimize absorption. 1, 2

Treatment Regimens by Clinical Presentation

CMV Retinitis (AIDS Patients)

• Induction therapy: 900 mg orally twice daily for 21 days 3, 2
• Maintenance therapy: 900 mg once daily indefinitely until immune recovery (CD4+ count >100 cells/µL sustained for 3-6 months) 3
• For sight-threatening lesions (adjacent to optic nerve or fovea): Consider ganciclovir intraocular implant plus oral valganciclovir, as this combination is superior to valganciclovir alone for preventing relapse 3
• For small peripheral lesions: Oral valganciclovir alone is adequate 3

CMV Colitis or Esophagitis

• Start with IV ganciclovir 5 mg/kg twice daily for 3-5 days to achieve rapid therapeutic levels when GI absorption may be compromised 1, 4, 5
• Switch to oral valganciclovir 900 mg twice daily once clinical improvement is observed and adequate GI absorption is assured 1, 4, 5
• Total treatment duration: 21-28 days or until complete symptom resolution 3, 1, 5

CMV Disease in Transplant Recipients

• Pre-emptive therapy: Valganciclovir and ganciclovir are the agents of choice for first-line treatment 3
• Oral valganciclovir is highly acceptable in allogeneic hematopoietic stem cell transplant recipients in the absence of substantial gastrointestinal GVHD (grades 3-4) 3, 4
• Critical contraindication: Do not use valganciclovir in liver transplant patients or those with hepatic dysfunction, as decreased cleavage of the valine ester limits conversion to active ganciclovir, resulting in higher rates of CMV disease 3, 1

CMV Neurologic Disease

• Initiate therapy promptly as this is critical for optimal clinical response 3
• Consider combination therapy with ganciclovir and foscarnet to stabilize disease and maximize response, though this carries substantial adverse effect rates 3

Criteria for Switching from IV to Oral Therapy

Switch from IV ganciclovir to oral valganciclovir when ALL of the following are met: 4

• Clinical improvement observed after 3-5 days of IV therapy (reduced symptoms, improved laboratory parameters)
• Adequate gastrointestinal absorption assured (no significant GI symptoms)
• No severe gastrointestinal GVHD (grades 3-4) in transplant patients
• Patient able to take oral medications reliably

Alternative Agents for Intolerance or Resistance

Second-Line Options

• Foscarnet is the primary alternative for patients who cannot tolerate ganciclovir due to neutropenia or thrombocytopenia 3, 5
• Foscarnet 90 mg/kg twice daily requires strict monitoring of renal function and electrolytes due to significant nephrotoxicity risk 5

Refractory or Resistant CMV

• Maribavir has shown promise for refractory or resistant CMV infections 3
• In phase III trials, maribavir achieved 56% CMV viremia clearance versus 24% with other agents (P<.001) 3
• Maribavir demonstrated less acute kidney injury versus foscarnet (8.5% vs 21.3%) and less neutropenia versus valganciclovir/ganciclovir (9.4% vs 33.9%) 3
• Cidofovir is reserved as third-line therapy due to substantial nephrotoxicity risk 5

Monitoring Requirements

During Induction Phase (First 3-5 Days)

• Complete blood count twice weekly 5
• Serum creatinine and electrolytes twice weekly 5
• Clinical symptom assessment 5

During Maintenance Phase

• Complete blood count weekly 5
• Renal function weekly 5
• CMV viral load by PCR or pp65 antigenemia weekly 4, 5
• For CMV retinitis: Regular ophthalmologic examinations 1, 4

Treatment Duration

• Continue treatment until CMV is no longer detectable by plasma NAT or pp65 antigenemia 4
• In HIV patients with retinitis, continue until immune recovery (CD4+ count >100 cells/µL for 3-6 months) 3

Critical Adverse Effects and Management

Hematologic Toxicity (Most Common)

• Severe leukopenia, neutropenia, anemia, thrombocytopenia can occur 2
• Dose reduction or interruption may be necessary in up to 40% of patients due to hematologic toxicity 1, 5
• Monitor CBC closely and adjust dose or switch to foscarnet if severe myelosuppression develops 3, 5

Other Adverse Effects

• Renal dysfunction (monitor creatinine regularly) 1
• Mild transaminase elevation 6
• Pancytopenia (rare but serious) 2, 6

Common Pitfalls to Avoid

1. Switching to oral therapy too early in patients with severe disease or questionable GI absorption leads to treatment failure 4
2. Using valganciclovir in liver transplant patients or those with hepatic dysfunction results in inadequate drug conversion and higher CMV disease rates 3, 1
3. Inadequate dose adjustment in renal impairment increases toxicity risk 4
4. Premature discontinuation before viral clearance leads to early recurrence 4, 6
5. Failure to monitor for neutropenia can result in severe complications requiring dose modification 4
6. Not considering substantial GI GVHD (grades 3-4) as a contraindication to oral therapy in transplant patients 3, 4

Dosing Considerations

Standard Adult Dosing

• All doses should be taken with food to optimize absorption 2
• Induction: 900 mg (two 450 mg tablets) orally twice daily 2
• Maintenance: 900 mg (two 450 mg tablets) orally once daily 2
• Adjust doses for renal function according to creatinine clearance 2

Prophylaxis in Transplant Recipients

• Heart or kidney-pancreas transplant: 900 mg once daily starting within 10 days of transplantation until 100 days post-transplantation 2
• Kidney transplant: 900 mg once daily starting within 10 days of transplantation until 200 days post-transplantation 2