Anti-Cytomegalovirus

Question 1

Anti-Cytomegalovirus Agents

Answer 1

Gangciclovir
Valgangciclovir
Foscarnet
Cidofovir

CMV- usually asymptomatic in normal individuals; can be devastating in immunocompromised

60% of Americans become seropositive by adulthood; infection is lifelong
If patient becomes compromised, infection can reactivate

Drugs work by preventing viral replication
Have appreciable toxicity

Question 2

Anti-Cytomegalovirus MOA

Answer 2

Gangciclovir- nucleoside analogue- after phosphorylation is integrated into viral DNA by DNA polymerase- halts viral replication

Valgangciclovir- pro drug

Cidofovir- nucleotide analogue with similar MOA

Foscarnet- pyrophosphate analogue- acts as a non competitive of DNA and RNA polymerase of multiple viruses

Question 3

Anti-Cytomegalovirus Spectrum

Answer 3

Good
CMV
HSV 1 and 2
VZV
EBV

Poor
HIV

Question 4

Anti-Cytomegalovirus Adverse Effects

Answer 4

Gang and Valgang have same reactions
Dose dependent myelosuppression that is relatively common (especially in higher doses or in renally impaired patients without dose adjustment)

Foscarnet- nephro and neurotoxic (reserved for patients who have failed other therapies)

N/V/D can occur from any agents

Foscarnet can cause penile ulcers

Cidofovir is uncommonly used; also had nephrotoxicity

Question 5

Anti-Cytomegalovirus Important Facts

Answer 5

Oral gang replaced by valgang (better bioavailability)

Gang- carefully dose by weight and renal function; when on therapy monitor for renal function changes

Valgang package insert specifies dose adjustment for renal dysfunction but not weight
(Also comes as 450mg); 900mg BID considered equivalent to 5mg/kg q12h of IV gang (may be much more than that for underweight patient because about 60% bioavailable (could possibly receive double the intended dose)

Extensive pre hydration regimens required with normal saline for foscarnet and cidofovir due to nephrotoxicity
Cidofovir requires coadministration with probenecid (attenuates toxicity by reducing excretion of cidofovir into renal tubules)

Genotype based susceptibility testing available for CMV (takes a while)- usually performed if resistance suspected in patients not responding to gang
Will reveal gang resistance and whether foscarnet or cidofovir are options

Valgang (is an oral and because of good bioavailability) requires monitoring for adverse effects that is just as rigorous as for IV gang
Consider dose reduction in underweight patient, especially if at high risk of toxicity

Question 6

Anti-Cytomegalovirus Good For

Answer 6

Gang and Valgang first line for treatment and prevention of CMV

Valgang often given to prevent CMV infections after transplant

Foscarnet is second line for CMV; can also be used for severe or resistant HSV infections

Cidofovir is second line for CMV