What is the next step in managing a patient with multiple myeloma and a compromised immune system who is not responding to oral antiviral therapy?

Management of Herpes Zoster Reactivation in Multiple Myeloma Patients Not Responding to Oral Antivirals

When oral antiviral therapy (acyclovir or valacyclovir) fails to control active herpes zoster infection in a multiple myeloma patient, switch immediately to intravenous foscarnet, as this is the definitive treatment for acyclovir-resistant herpes simplex virus infections in immunocompromised patients. 1

Immediate Treatment Protocol

• Initiate IV foscarnet at 40 mg/kg every 8 or 12 hours for 2-3 weeks or until complete healing occurs 1
• Administer foscarnet via controlled intravenous infusion at a rate not exceeding 1 mg/kg/minute using an infusion pump 1
• Provide aggressive hydration with 750-1000 mL normal saline or 5% dextrose prior to the first foscarnet infusion to establish diuresis and minimize nephrotoxicity 1
• Continue hydration with 500 mL of fluid concurrent with each 40-60 mg/kg dose of foscarnet 1

Critical Monitoring Requirements

• Calculate creatinine clearance (mL/min/kg) at baseline and frequently thereafter, even if serum creatinine is within normal range, as dose adjustments are mandatory based on renal function 1
• Monitor serum calcium, magnesium, potassium, and phosphate levels closely, as foscarnet causes electrolyte disturbances including severe hypocalcemia 1
• Discontinue foscarnet if creatinine clearance falls below 0.4 mL/min/kg, hydrate the patient, and monitor daily until renal function recovers 1
• Watch for symptoms of hypocalcemia including perioral tingling, numbness in extremities, or paresthesias during or after infusion—stop infusion immediately if these occur 1

Why Oral Antivirals Fail in This Population

• Multiple myeloma patients have a 10-fold higher risk for viral infections compared to healthy individuals due to disease-inherent immune suppression 2, 3
• The immunocompromised state in myeloma results from B-cell dysfunction, impaired T-cell and NK cell function, and functional hypogammaglobulinemia 3, 4
• Treatment with proteasome inhibitors and immunomodulatory drugs further compounds immunosuppression, creating conditions where acyclovir-resistant viral strains emerge 5, 4
• Repeated treatment with standard antivirals can lead to development of resistance associated with poorer therapeutic response 1

Drug Interactions and Contraindications to Avoid

• Avoid concurrent use of foscarnet with potentially nephrotoxic drugs including aminoglycosides, amphotericin B, cyclosporine, acyclovir, methotrexate, tacrolimus, and intravenous pentamidine 1
• Do not administer foscarnet concurrently with intravenous pentamidine due to risk of severe, potentially fatal hypocalcemia 1
• Avoid foscarnet in combination with drugs that prolong QT interval (Class IA/III antiarrhythmics, phenothiazines, tricyclic antidepressants, certain macrolides and fluoroquinolones) due to risk of torsades de pointes 1
• Foscarnet is chemically incompatible with 30% dextrose, amphotericin B, calcium-containing solutions (Ringer's lactate, TPN), acyclovir sodium, ganciclovir, and multiple other IV drugs—never mix in the same catheter 1

Route of Administration Considerations

• Use central venous line when possible to administer the standard 24 mg/mL foscarnet solution 1
• If peripheral vein catheter must be used, dilute foscarnet to 12 mg/mL concentration with 5% dextrose or normal saline to avoid local vein irritation 1
• Infuse only into veins with adequate blood flow to permit rapid dilution and distribution 1

Prevention of Future Episodes

• Once the acute infection resolves, ensure the patient receives the recombinant VZV glycoprotein E vaccine (Shingrix) rather than live-attenuated vaccine, as live vaccines are contraindicated in myeloma patients on immunosuppressive therapy 2, 5
• Shingrix achieves 80.4% antibody response in myeloma patients and requires two doses given 2-6 months apart 2, 6
• Resume prophylactic acyclovir or valacyclovir after acute infection resolves, continuing for six weeks after discontinuation of proteasome inhibitor therapy 2, 5
• All multiple myeloma patients receiving proteasome inhibitor-based therapies must receive herpes zoster prophylaxis—this is a Grade 1A recommendation 2, 5

Common Pitfalls

• Do not continue oral antivirals when clinical failure is evident—this delays effective treatment and allows progressive tissue damage 5
• Do not use live-attenuated varicella-zoster vaccine (Zostavax) in active myeloma patients, as this is contraindicated and carries risk of vaccine-strain infection 2, 5
• Do not overlook the need for aggressive hydration with foscarnet, as nephrotoxicity is the major dose-limiting toxicity 1
• Do not administer foscarnet in patients with cardiomyopathy or those on controlled sodium diets without careful consideration, as foscarnet contains 5.5 mg sodium per mL 1