- Requires tri-phosphorylation for
activation
- competitively inhibits
viral DNA polymerase
- in CMV-infected cells:
first phosphorylation step catalyzed by
viral specific protein kinase
- in HSV-infected cells:
first phosphorylation step catalyzed by
thymidine kinase
- Ganciclovir (DHPG, Cytovene) has
activity against: HSV, VZV, CMV, and EBV
- Activity against CMV much greater
than that of acyclovir
- Ganciclovir (DHPG, Cytovene)
resistance due to either DNA polymerase mutations
or protein kinase mutation
- IV and oral route of
administration
- renal clearance varies in a manner
proportional to creatinine clearance
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Ganciclovir: (DHPG, Cytovene):Clinical Use
- IV ganciclovir indicated for CMV
retinitis in HIV patients.
- Intraocular
implant releasing ganciclovir
(Vitrasert) appears more
effective then I'd be ganciclovir
(DHPG, Cytovene) for the eye with
the implant (not effective in the
other eye or systemically)
- In AIDS patients not
taking a protease
inhibitor, using the
implant plus high-dose
oral drug decreases the
risk of contralateral
retinitis and extraocular
CMV disease
- Oral or IV ganciclovir (DHPG,
Cytovene) followed by high-dose acyclovir
(Zovirax) (oral) reduces CMV disease risk
in patients who have orthotopic liver
transplantation
- Oral ganciclovir
(DHPG, Cytovene) (three months)
is better then oral acyclovir
(Zovirax) for CMV
infection/disease prevention
patients receiving seropositive
kidney transplants
- IV ganciclovir indicated for
CMV pneumonitis in patients with
compromised immune systems.
- Also used in other
CMV-associated disease, including
esophagogastrointestinal
infection, hepatitis and
"wasting" illness
- IV ganciclovir may be used to
treat CMV colitis and esophagitis
- Oral ganciclovir may be used
to prevent and/or in CMV disease in AIDS
patients and for maintenance therapy of
CMV retinitis
- Oral form less
effective in maintenance
treatment for AIDS patients with
CMV retinitis, compared to IV
form.
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Ganciclovir: (DHPG, Cytovene):Adverse Reactions
- Teratogenic, carcinogenic
& mutagenic agent
- Most common:
myelosuppression, notably neutropenia:
bone marrow suppression limits this
drug's use in many patients.
- granulocytopenia
& thrombocytopenia: more
common with IV formulation
{typically reversible}
- Severe myelosuppression may be
seen in patients receiving ganciclovir
(DHPG, Cytovene) along with
- zidovudine
(Retrovir, AZT, azidothymidine)
- azathioprine (Imuran)
- or
mycophenolate mofetil.
- Ganciclovir (DHPG,
Cytovene)-induced neutropenia may
be treated with GM CSF; G-CSF [granulocyte-colony-stimulation
factors]
- Unusual CNS toxicity may
include headache, seizures, altered
mental status.
- Resistance:
- ganciclovir
(DHPG, Cytovene) resistance
associated with:
- persistent diarrhea
- progressive
disease
- approximately
20% of organ transplant
recipients who fail oral
ganciclovir (DHPG,
Cytovene) prophylaxis
excrete ganciclovir (DHPG, Cytovene)-resistant virus
- Ganciclovir
(DHPG, Cytovene)-resistant CMV
strains may be responsive to
cidofovir (Vistide) or foscarnet (Foscavir)
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