Treatment regimens for adult patients with cytomegalovirus (CMV) retinitis

Drug	Induction	Maintenance*	Laboratory monitoring^¶	Dose-limiting toxicity (percent of patients)
Primary regimen
Oral valganciclovir^Δ	900 mg every 12 hours with food for 14-21 days	900 mg once per day with food	Complete blood count (CBC) twice/week during induction, weekly during maintenance; Serum creatinine monthly	Neutropenia^◊, thrombocytopenia^§, diarrhea
If retinal lesions are immediately sight-threatening ADD intravitreal ganciclovir or foscarnet^¥
Ganciclovir
Intraocular implants	Ganciclovir surgically implanted reservoir is an effective treatment, but is no longer available
Intravitreal injection^¥	Single injection^‡: 2.5 mg per injection (in 0.05 mL volume) in combination with oral valganciclovir^† OR Repeated injections: 2.5 mg per injection (in 0.05 mL volume) weekly for two to three weeks in combination with oral valganciclovir^†	Oral valganciclovir^† OR Intravitreal ganciclovir 2.5 mg (in 0.05 mL volume) per week in settings where systemic therapy is unavailable^**	Not applicable	Direct retinal toxicity if doses are excessively high
Foscarnet
Intravitreal injection^¥	Single injection^‡: 2.4 mg per injection in combination with oral valganciclovir^† OR Repeated injections: 2.4 mg per injection given twice weekly for up to 4 doses over a period of 7 to 14 days in combination with oral valganciclovir^†	Oral valganciclovir^†	Not applicable	Direct retinal toxicity if doses are excessively high
Alternate systemic regimens for patients unable to take oral valganciclovir. If retinal lesions are sight-threatening, ADD intravitreal ganciclovir or foscarnet, as above^¥
Intravenous (IV) ganciclovir^Δ
Standard dose	5 mg/kg IV every 12 hours for 14-21 days	5 mg/kg IV per day OR Oral valganciclovir as above	Complete blood count (CBC), serum electrolytes twice per week during induction and once weekly during maintenance; serum creatinine monthly	Neutropenia (15-50)^◊, thrombocytopenia (5-20)^§
High dose (salvage therapy)	5 to 7.5 mg/kg IV every 12 hours for 14-21 days	10 mg/kg IV per day		Neutropenia (15-50)^◊, thrombocytopenia (5-20)^§
Intravenous (IV) foscarnet^¶¶
Standard dose	60 mg/kg IV every 8 hours or 90 mg/kg IV every 12 hours for 14-21 days	90 mg/kg IV per day OR Oral valganciclovir as above	CBC with differential, platelet count, serum creatinine, potassium, magnesium, ionized calcium, phosphorous twice per week during induction, weekly during maintenance; hemoglobin	Nephrotoxicity (10-20), infusion-related decreased ionized serum calcium^ΔΔ, other electrolyte abnormalities, genital ulcers, fluid overload, anemia
High dose (salvage therapy)	90 mg/kg IV every 12 hours for 14-21 days	120 mg/kg IV per day	Same as for standard dose foscarnet
Ganciclovir^Δ and foscarnet^¶¶ (salvage therapy)	90 mg foscarnet/kg IV every 12 hours PLUS either 5 mg ganciclovir/kg IV per day or oral valganciclovir 900 mg per day for 14-21 days OR 5 mg ganciclovir/kg IV every 12 hours (OR oral valganciclovir 900 mg twice daily) plus 90 mg foscarnet/kg IV per day for 14-21 days	5 mg ganciclovir/kg IV per day (OR oral valganciclovir 900 mg daily) plus 90 mg foscarnet/kg IV per day	Refer to individual agents above	Refer to individual agents above
Cidofovir (IV)^◊◊	5 mg/kg IV once per week for 2 weeks	5 mg/kg IV once every other week	Serum creatinine, urinary protein CBC with differential, platelets, and hepatic transaminases before each infusion	Nephrotoxicity (50), proteinuria, neutropenia^◊, decreased intraocular pressure^§§, iritis^§§, uveitis^§§, neuropathy; nausea, fever, rash (associated with probenecid)

CMV retinitis should be managed in consultation with an experienced ophthalmologist.

* Maintenance with oral valganciclovir is preferred. Considerations for decision to stop maintenance are reviewed in the topic on the treatment of CMV retinitis.
¶Monitoring may be less frequent in resource-limited settings. Refer to the topic on treatment of CMV retinitis for a discussion.
Δ The dose of oral valganciclovir or IV ganciclovir should be adjusted for renal insufficiency; for detail, refer to Lexicomp drug monograph included within UpToDate.
◊ Neutropenia is reversible with granulocyte colony-stimulating factor (GCSF) given as adjunctive treatment. Refer to the topic on the treatment of CMV retinitis.
§ Ganciclovir should be stopped for platelet counts <20,000 per microL. Avoid or use caution with other myelosuppressive agents.
¥ The preferred use of intravitreal injections is in the setting of immediately sight threatening lesions in conjunction with systemic therapy. In resource-limited settings, where systemic therapy may not be available, the frequency of dosing is described in the table. A detailed discussion of intravitreal therapy for CMV retinitis is found in the topic on treatment of CMV retinitis.
‡ If systemic therapy is initiated within 24 hours of the initial intravitreal injection, subsequent injections are probably unnecessary.
†For patients who cannot take oral valganciclovir, an alternate systemic therapy should be used as described in the table.
** Local treatment alone will not prevent involvement of other eye or additional systems. Refer to the topic on treatment of CMV retinitis.
¶¶ Precise adjustment of foscarnet dose for renal insufficiency is necessary. An infusion pump is used to assure appropriate (ie, 2 hour) infusion time. (For detail refer to Lexicomp drug monograph included with UpToDate). Hydration is recommended to reduce the risk of nephrotoxicity. Infuse 750-1000 mL of normal saline prior to the first infusion of foscarnet to establish diuresis. With subsequent infusions, 750-1000 mL of hydration fluid should be given concurrently with each 90-120 mg/kg infusion of foscarnet.
ΔΔ Symptoms of infusion-related ionized hypocalcemia include tetany, paresthesias, arrhythmia, mental status changes, and headache. If this occurs, the infusion should be slowed. Avoid co-treatment with other nephrotoxic drugs and drugs that can alter serum calcium concentrations (ie, pentamidine). Severe additive toxicity and deaths have been reported.
◊◊ Cidofovir use is contraindicated in patients with pre-existing renal insufficiency or proteinuria. In addition, cidofovir should be avoided in patients with a sulfa allergy because of cross hypersensitivity with probenecid. To decrease cidofovir associated nephrotoxicity, administer 2 g probenecid orally 3 hours before cidofovir infusion and hydrate with 1 L normal saline 1 hour prior to infusion. Administer 1 L normal saline with or immediately after cidofovir infusion. Administer 1 g probenecid orally 2 and 8 hours after infusion is completed. Probenecid is associated with hypersensitivity reactions and intolerance (ie, nausea, vomiting, fever). Dose should be reduced from 5 to 3 mg/kg if serum creatinine level increases by 0.3 to 0.4 mg/dL (26.5 to 35.4 micromol/L) over baseline value. Drug must be discontinued if serum creatinine level increases by >0.5 mg/dL (44 micromol/L) over baseline value or if urinary protein level is >3+. Cidofovir should not be administered concurrently with or within 7 days of other nephrotoxins.
§§ Discontinue cidofovir if intraocular pressure is below 50 percent of baseline value or if uveitis develops that is unresponsive to topical corticosteroids and cycloplegics.

Adapted from:

Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Available at https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-opportunistic-infection/cytomegalovirus-disease?view=full.

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Treatment regimens for adult patients with cytomegalovirus (CMV) retinitis