Valganciclovir

	Zambia HIV National Guidelines
	Introduction HIV Counseling and Testing Sexually Transmitted Infections (STIs) General Principles of Antiretroviral Therapy for Chronic HIV Infection in Adults and Adolescents When to Start ARV Therapy for Chronic HIV Infection in Adults and Adolescents Initial Regimen for ARV Therapy Adherence Baseline evaluation and Monitoring Calculations: Ideal Body Weight, Body Mass Index and Creatinine Clearance ARV Therapy for Individuals with Tuberculosis Co-Infection Adverse Effects and Toxicity Immune Reconstitution Inflammatory Syndrome (IRIS) Changing or Stopping ART Treatment Failure Stopping ARV Therapy Post Exposure Prophylaxis Cotrimoxazole Prophylaxis WHO Staging in Adults and Adolescents Nutrition Care and Support Palliative Care in HIV and AIDS
	Guide Editors
	Editor In Chief Joel E. Gallant, MD, MPH Pharmacology Editor Paul Pham, PharmD, BCPS Zambia Guideline Team Peter Mwaba MMed PhD FRCP Alywn Mwinga MMed Isaac Zulu MMed MPH Velepie Mtonga MMed Albert Mwango MBChB Jabbin Mulwanda MMed FCS

Drugs>Antimicrobial Agents>

Valganciclovir

Paul A. Pham Pharm.D. and John G. Bartlett M.D.
01-11-2010

Zambia Specific Information

Available formulation in Zambia: tablet: 450 mg
Oral valganciclovir equivalent to IV ganciclovir for treatment of CMV disease.
Due to additive bone marrow suppression, avoid co-administration with AZT.

Zambia Information Author: Paul A. Pham, Pharm.D.

INDICATIONS

FDA

Treatment of CMV retinitis in pts with AIDS.
Prevention of CMV disease in kidney, heart, and kidney-pancreas transplant pts at high risk for CMV disease (e.g., donor positive, recipient negative). Not indicated in liver transplant pts.

NON-FDA APPROVED USES

Prevention of CMV retinitis of the contralateral eye in pts treated with intraocular ganciclovir implant.
Treatment of GI CMV disease (in pts tolerating PO intake).

FORMS

brand name	generic	Mfg	brand forms	cost*
Valcyte	Valganciclovir	Roche	oral tablet 450 mg	$42.83

*Prices represent cost per unit specified and are representative of "Average Wholesale Price" (AWP). AWP Prices were obtained and gathered by Lakshmi Vasist Pharm D using the Red Book, manufacturer's information, and the McKesson database.

^Dosage is indicated in mg unless otherwise noted.

USUAL ADULT DOSING

CMV retinitis (induction): 900 mg PO twice-daily with food x 3 wks (plus ganciclovir implant)
CMV retinitis (maintenance): 900 mg PO once-daily with food until immune reconstitution (CD4 >150 x 3-6 mos w/ ophthalmology consultation confirming quiescence).
Gastrointestinal CMV disease: 900 mg twice-daily with food x 3-6 wks (consider maintenance therapy with severe disease and/or with relapse)
Prevention of CMV disease in kidney, heart, and kidney-pancreas transplant pts at high risk for CMV disease (e.g., donor [+] CMV/recipient negative): 900 mg daily with food beginning within 10 days of transplantation and continuing through day 100 post-transplantation.
Monitor CBC 2-3x/wk. Discontinue drug or add G-CSF if ANC <500. Discontinue if platelet count <25,000 or consider D/C if Hgb <8g/dL.

RENAL DOSING

DOSING FOR GLOMERULAR FILTRATION OF 50-80

>60 ml/min: 900 mg (induction); 900 mg once-daily (maintenance).

DOSING FOR GLOMERULAR FILTRATION OF 10-50

40-59 ml/min: 450 mg twice-daily (induction) then 450mg once-daily (maintenance). 25-39 ml/min: 450 mg once-daily (induction) then 450 mg every other day (maintenance). 10-24 ml/min: 450 mg every other day (induction) then 450 mg twice weekly (maintenance).

DOSING FOR GLOMERULAR FILTRATION OF <10 ML/MIN

Not recommended by manufacturer.

DOSING IN HEMODIALYSIS

Not recommended by manufacturer (HD removes approx. 50% of GCV). Consider using 1.25 mg/kg IV ganciclovir post-HD (induction)

DOSING IN PERITONEAL DIALYSIS

No data.

DOSING IN HEMOFILTRATION

No data.

ADVERSE DRUG REACTIONS

COMMON

Neutropenia (reversible and responds to G-CSF). Reversible within 3-7 d of discontinuation or dose reduction.
Reversible thrombocytopenia
Diarrhea and nausea

OCCASIONAL

Anemia
Fever
Rash
Headache
Seizures
Confusion
Mental status changes

RARE

Hepatoxicity

DRUG INTERACTIONS

ddI (buffered or EC): not studied with valganciclovir but ddI levels may be increased. PK study with ddI (buffered) and ganciclovir (GCV) resulted in a 111% increase in ddI AUC. GCV AUC decreased by 21%. Monitor closely for ddI toxicity. Consider ddI dose reduction or alternative NRTI.
Drug Interactions with PIs, NNRTIs, RAL, MVC, and ENF unlikely.
Myelosuppressive drugs (e.g., AZT, interferon, 5-FC, pyrimethamine, etc.): may increase risk of hematologic toxicity. Monitor closely with co-administration. Consider alternative agents or support with GCSF.
Probenecid: may increase GCV serum levels. Monitor for GCV toxicity.
Trimethoprim: may increase GCV serum levels. Monitor for GCV toxicity.

SPECTRUM

CMV, HSV-1, HSV-2, EBV, VZV, HHV-8, and HHV-6.

PHARMACOLOGY

Pharmacology

COMMENTS

Oral valganciclovir has 10-fold better absorption than oral GCV. AUC of oral valganciclovir 900 mg comparable to GCV 5mg/kg IV. Oral valganciclovir equivalent to IV GCV for treatment of CMV retinitis in HIV+ pts and is preferred due to oral administration. Contraindicated by manufacturer in pts with severe neutropenia (ANC <500/dL), thrombocytopenia (<25,000/dL), severe anemia (Hgb <8 g/dL) and renal failure. Neutropenia and anemia generally responsive to G-CSF and erythropoietin.

Basis for Recommendations

Recommendations of the National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC), and the HIV Medicine Association of the Infectious Diseases Society of America (HIVMA/IDSA) ; Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents ; http://AIDSinfo.nih.gov ; 2008 ; Vol.
Rating: Basis for recommendation
Comments:In pts tolerating PO intake, oral valganciclovir + ganciclovir implant is recommended for the treatment of CMV retinitis.

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Abbreviations