Antiviral Agents

1. ANTIVIRAL AGENTS

2. Introduction
 Antiviral agents are a class of medication
used specifically for treating viral infections.
 Specific Antivirals are used for specific
viruses.
 Antivirals do not destroy their target
pathogen, instead they inhibit their
replication.

3. Classification
 Anti herpesvirus agents
1. Acyclovir
2. Valaciclovir
3. Famciclovir
4. Penciclovir
5. Cidofovir
6. Foscarnet
7. Ganciclovir
8. Idoxuridine
9. Trifluridine
10. Vidarabine

4. Anti Influenza agents
1. Amantadine
2. Oseltamivir
3. Rimantadine
4. Zanamivir

5. Anti Retrovirus Agents
 NRTIs:-
Zidovudine,Didanosine,Zalcitabine,Stavudine,Lam
ivudine,Abacavir,Emtricitabine
 Nucleotide RTI- Tenofovir
 NNRTIs:- Nevirapine, Efavirenz, Delavirdine
 PIs:-Ritonavir, Indinavir, Saquinavir, Nelfinavir,
Lopinavir
 Fusion inhibitor – enfuviritide
 Entry inhibitor - Maraviroc
 Integrase inhibitor - Raltegravir

6. Other antiviral agents
1. Fomivirsen
2. Imiquimod
3. Interferon-alfa
4. Lamivudine
5. Ribavarin

7. ANTI HERPESVIRUS
DRUGS

8. Acyclovir
Valacyclovir
Famciclovir

9. ACYCLOVIR VALACYCLOVIR FAMCICLOVIR
PEAK LEVEL 1.5-2 h uncertain 0.9 h
BIOAVAILABILITY
(%)
15-30 55 77
PROTEIN BINDING
(%)
9-33 13.5- 17.9 < 20
HALF LIFE 1.3-1.5 h 2.5 – 3.3 h 2.3- 3 h
METABOLISM No hepatic
metabolism
Conversion to
acyclovir
Conversion to
penciclovir
EXCRETION Urine
feces
Urine
feces
73% urine
27% feces

11. Acyclovir
 Acyclovir is a acyclic guanine
nucleoside analog.
 Available as oral, iv & topical (5%).

12.  Spectrum of activity
o Most effective against HSV-1 and
HSV-2
o Less effective against VZV
o Not effective against CMV (does not
encode TK)

13. Acyclovir:-Therapeutic Uses
FDA APPROVED
 Herpes simplex infections
primary episode:- oral
200mg x 5times/day x 7-10 days or
400mg x 3 times / day x10 days.
recurrent episodes:- oral
200mgx 5times/day x 5 days or
400mg x3 times/day x5 days.
suppressive therapy:- oral
400mgx BD for 1-2 years

14.  Varicella- zoster Infections
Chicken pox :- oral
20mg/kg/dose(max.800mg) x 4
times/day x 7 days
Herpes-zoster:- oral
800mg x 5times/day x 7-10 days

15.  HSV encephalitis: iv
10mg/kg /8 hrly x10 days
 Neonatal HSV infections iv
15-20 mg/kg/8hrly x 14 - 21 day
 ICS :- 400mg 5 times for 14-21 days

16. Acyclovir:- Off Lable uses-
 Recurrent erythema multiforme
(proven/ presumed d/t HSV)- 20-
25mg/kg daily
 Other subsets of HSV infections:-
Primary gingivostomatitis, recurrent
herpes labialis, herpes gladiatorum,
eczema herpeticum, herpetic whitlow and
herpetic keratoconjunctivitis.

17. I V Acyclovir
Indications-
 Disseminated HSV
 Neonatal infection
 Eczema herpeticum
 Herpes encephalitis.
 ICS with VZV

18. Prophylaxis in UV induced HSV
 Acyclovir 400mg bid 7 days before or
5 min after UV exposure

19. Post exposure prophylaxis-
Indications-
 Neonates when mother develop
varicella within 7 days before to 7
days after delivery
 Immunosuppressed children & adults
 Non immune pregnant women
 Preterm infants
 Patient receiving chronic chemotherapy

20.  High risk pt should receive passive
immunization with VZV specific
immunoglobulin within 96 hr of
exposure.
 For those who missed 96 hr window
for Ig ,high dose ACV (40-80
mg/kg/day x 7 days) is recommended.

21. Acyclovir: Therapeutic Effects
 HSV infection:- reduction in
asymptomatic viral shedding,
symptoms, and time to healing but no
reduction in risk of recurrent genital
lesions
 Immunocompromised pts:- shortens
healing time, duration of pain, period
of virus shedding

22.  Varicella :- reduces time to crusting of
lesions, no. of lesions and duration of
fever when initiated within 24 – 72 hr
 Zoster ophthalmicus:- reduction in ocular
complications

23.  Herpes zoster :- increased healing time
when initiated within 1-2 days, reduces
duration of PHN, no. of new lesions &
duration of fever, rash & constitutional
symptoms

24. Acyclovir: Adverse Effects
 Generally well tolerated
 Oral – infrequently nausea, vomiting,
diarrhea, rash, headache,
 very rarely- renal insufficiency,
neurotoxicity

25. Renal insufficiency- (5%) Reversible.
 Crystallization in renal tubules –
obstructive nephropathy.
 Treated by adequate hydration & slow
iv infusion over a period of 1 hr.

26.  Neurotoxicity - (1%).
Altered sensorium, tremors, myoclonus,
seizures, Hemodialysis if severe
 Neutropenia
 Hepatotoxicity

27. Acyclovir dose adjustment for
renal impairment

28. Creatinine Clearance
 Creatinine clearance rate ( CrCl) is the
volume of blood plasma that cleared of
creatinine per unit time and is useful
measure of GFR.
 Cockcroft-Gault Formula for CrCl -
CrCl = ( 140- age) * Mass ( in Kgs) * constant
____________________________
Serum creatinine in micromol/L
Constant = 1.23 for Men and 1.04 in women
Normal range – 97-137 ml/min/1.73 m2 ( Men)

29. INTRAVENOUS
CREATININE
CLEARANCE
( ml/min)
DOSE
25-50 Normal dose every 12
hrs
10-25 Normal dose every 12
hrs
< 10 50% of normal dose
every 24 hrs

30. ORAL
Crcl
(ml/min)
DOSE
25-50 NORMAL
10-25 SIMPLEX- 200mg TDS-
QDS
ZOSTER – 400- 800mg tds
< 10 SIMPLEX- 200 mg BD
ZOSTER- 400-800 mg BD

31. Acyclovir: contraindications
 Hypersensitivity to acyclovir
 Hypersensitivity to any component of
formulation
 Pregnancy – category B

32. Acyclovir : Resistance
 Absence or partial production of
thymidine kinase : most common
 Altered thymidine kinase substrate
specificity
 Altered viral DNA polymerase

33. Topical acyclovir
Indications :
1. Genital herpes simplex infection :
5% ointment 4 times a day for 7 days
for Initial genital herpes infections .
Useful in-
promoting healing
relieving pain
reducing viral shedding.
Less useful in recurrent episodes.
2. Recurrent herpes labialis (cold sores) :
5% ointment 5 times a day for 4 days

34. 3. Limited mucocutaneous herpes simplex
infections in immunocompromised patients
 Therapy should be initiated as early as
possible.
 Rubber gloves used while applying the
medication - to prevent autoinnoculation /
transmission to others

35. Acyclovir available as:-
 ACIVIR dispertab (CIPLA) 200 mg (63.13 INR)
400 mg (60.99 INR)
800 mg (104.86 INR)
 CIVIR dispertab (BIOMAX) 400 mg (1300 INR)
800 mg (2300 INR)
 ZOVIRAX tab (GSK) 200 mg (42.8 INR)
400 mg (156.6 INR)
800 mg (161.7 INR)
 HERPERAX tab 200mg (42 INR)
(MICRO GRATIA) 400 mg (160 INR)
800mg (300 INR)

36.  OCUVIR dispertab 200 mg (57.4 INR)
(FDC LUMINA ) 400 mg (60.9 INR)
800 mg (99.5 INR)
 ZOVIRAX susp (GSK) 400 mg x 5 mL
(236.4 INR)
 ACIVIR vial (CIPLA) 25 mg x 10ml (321 INR)
 ZOVIRAX vial (GSK) 250 mg x 10 mL
(840 INR)

37.  ACIVIR cream (CIPLA) 5 % w/w x 5g
(42.8 INR)
 OCUVIR cream (LUMINA) 5 % w/w x 5g
(41.1 INR)
 HERPERAX oint (Micro Gratia) 5 % w/w x 5g
(54 INR)
 HERPERAX cream (Micro Gratia) 5 % w/w x 5g
(50 INR)
 ACIVIR OINT oint (CIPLA) 3 % w/w x 5g (42.1 INR)

38. Valacyclovir
Prodrug of acyclovir.
 Available as oral form only
 Sr. level 3-4 times greater than oral
ACV
Approximates those with I.V. ACV
 Convenient dosage schedule – better
compliance.

39. Valacyclovir:-Therapeutic uses
FDA APPROVED
 Herpes simplex infections
Primary episode: 1gm BD x 10 days
Recurrent episodes: 500mg BD x 3 days
Immunocompromised:500mg BD x 7
days
Suppressive therapy:
< 9 episodes/yr- 500mg
OD
>9 episodes/yr- 1 gm OD

40.  Herpes zoster -
1 gm x tds for 7 days.
 Immunocompromised with VZV-
500 mg BD for 7 days.

41. Valacyclovir:- Off label uses -
 Recurrent erythema multiforme
 Other subsets of HSV infections:
primary gingivostomatitis, recurrent
herpes labialis, herpes gladiatorum,
eczema herpeticum, herpetic whitlow and
herpetic keratoconjunctivitis.

42. Valacyclovir:- Therapeutic effects
 HSV infection:- reduction in virus
shedding, symptoms, and time to healing.
 Recurrent genital HSV episodes:-
shortens manifestations by 1-2 days.
Asymptomatic shedding and transmission
may occur.

43.  Immunocompromised patients:-
shortens healing time, duration of pain (
more than acyclovir), period of virus
shedding
 More efficacious than ACV in
ameliorating PHN.

44. ADVERSE EFFECTS
 Nausea and headache ( as with ACV)
 Thrombotic thrombocytopenic purpura
/
Hemolytic uremic syndrome ( in pt
with advanced HIV disease and in
transplant recipients receiving
dosages of 8g/day).

45. Famciclovir and Penciclovir
 Penciclovir :- acyclic guanine
nucleoside analog
 Famciclovir :- diacetyl ester prodrug of
6- deoxypenciclovir
 Similar to acyclovir in potency and
spectrum of activity.

46. Famciclovir
 Prodrug of penciclovir
 Available as oral form only.
 Prolonged T1/2 :
- 10-20hrs HSV infected &
- 7 hrs VZV-infected cells, so prolonged antiviral
effects.
(ACV -has < 1 hour in HSV & VZV infected cells)

47. Famciclovir:- therapeutic uses
FDA APPROVED – HSV infections
 1st episode :- 250mg TDS x 7-10 days
 Recurrent:- 125mg BD x 5 days
 Suppression:- 250mg BD (500mg BD
in HIV infected)
 Herpes Zoster :- 500 mg TDS x7- 10 days

48. Famciclovir:- Off lable uses
 Other subsets of HSV infections:
Primary Gingivostomatitis, recurrent
herpes labialis, herpes gladiatorum,
eczema herpeticum, herpetic whitlow and
herpetic keratoconjunctivitis.

49. Famciclovir : adverse effects
 Well tolerated
 Associated with headache, diarrhea,
nausea
 Hallucinations and confusion -rarely
( more in elderly)

50. Famciclovir : Contra-indications
 Hypersensitivity to famciclovir.
 Hypersensitivity to any component
of the formulation
 Pregnancy- Categary B drug.

51.  VALCIVIR tab (Cipla) -1 g (140 INR)
500 mg (87 INR)
 FAMTREX tab(Cipla) -250 mg (392 INR)
500 mg (280.75 INR)
 MICROVIR tab (Micro Gratia) - 250 mg (95 INR)
500 mg (149 INR
 FAMIRAX tab (Synmedic) - 250 mg x 100's
500 mg x 100's

52. -Only in topical preparation .
- Oral bioavailability is limited.
 Advantages over Acyclovir are-
1. More efficient phosphorylation,
2. Higher affinity of viral DNA polymerases for the
triphosphate form
3. Increased stability of the triphosphate form (longer
duration of activity)- so preferred over ACV if oral
therapy is not possible / contraindicated
Penciclovir

53. 1% cream (Denavir- Denco Asset US)
approved for treatment of recurrent
herpes labialis in 12 yrs of age or older.
 Application: every 2 hrs for 4 days
 Most common side effect - headache
 Pregnancy category B

54. Primary episode of HSV
 Acyclovir 400mg tid x 7- 10days
 Famciclovir 250mg tid x 7-10days
 Valacyclovir 1gm bid x 7- 10days

55. Episodic therapy in recurrent
HSV
 Acyclovir 400mg tid x 5days OR
800mg tid x 2days
 Famciclovir 125mg bid x 5days OR
1gm bid x 1days
 Valacyclovir 500mg bid x 3-5days

56. Suppressive therapy in ICS
 Acyclovir 400 bid
 Famciclovir 500mg bid
 Valacyclovir 500mg bid

57. CIDOFOVIR
 Nucleoside analogue of deoxycytidine
monophosphate
 Exerts activity against – HPV, HSV
 Available intravenously for CMV retinitis
in AIDS pts.
57

58. • Cidofovir Incorporated into cells
•
•
• Does not depend on viral thymidine kinase for its
phosphorylation.
• Cidofovir diphosphate acts as a competitive
inhibitor of deoxycytosine -5’- triphosphate for
incorporation into viral DNA by DNA
polymerases
• To a lesser extent also inhibits host cell DNA
58
2 stages of phosphorylation ( host cell
enzymes)
Cidofovir diphosphate

59.  Approved for intravenous
administration
 Plasma half life: 2.6 hrs
 Drug is excreted by kidney
 Has a markedly prolonged intracellular
half life ( more than 48 hrs )-
recommended dosing regimen of 5 mg
/ kg iv weekly for 1st 2 weeks
f/by
 one dose every 2 weeks.
59

60. FDA APPROVED
 CMV retinitis in AIDS
 Treatment of resistant HSV and CMV
infections
60

61.  Molluscum contagiosum
 Recalcitrant MC in HIV positive pt treated with
topical OR IV cidofovir.
 Application of 3% cidofovir cream daily from
Monday to Friday X 2 weeks results in 70%
clearance
 By 1 month complete resolution is seen
 Condyloma acuminata
 1% cream effective as mono / combination therapy
for resistant condyloma acuminata.
 Applied daily X 2-5 wks OR
 5 days in a week X 6 wks 61

62.  Verruca vulgaris
 Case reports – complete clearance with 3% cream
applied twice daily for 10 days
 Herpes simplex: acyclovir resistant HSV in
HIV/AIDS patients : Topical 3% gel
 In healthy pts with recurrent HSV cidofovir gel
1%,3%,5% used within 12 hrs of outbreak
decreased duration of episode and duration of
viral shedding.
62

63.  Other Uses
Two cases of successfully treated
BCC have been described
In addition , topical Cedofovir is
claimed to be more effective than
systemic for treating vaccinia in
immunocompromised mice
63

64. 64
CONDITION DOSAGE ROUTE DURATION
CMV retinitis Induction:
5mg/kg every
week
Maintenance: 5
mg/kg every 2
wks
IV
IV
2 weeks
Till CD4 count
> 100 / after 6
months of
HAART
Administer with probenecid 2 g orally 3 hours prior to each cidofovir dose
and 1 g at 2 hours and 8 hours after completion of the infusion (total: 4 g)
Hydrate with at least 1 L of 0.9% NS I.V. prior to each cidofovir infusion;
infuse saline over a 1- to 2-hour period immediately prior to cidofovir
infusion. A second liter may be administered over a 1- to 3-hour period at
the start of cidofovir infusion or immediately following infusion, if tolerated

65.  The maintenance dose of cidofovir
must be reduced from 5 mg/kg to 3
mg/kg for an increase in serum
creatinine of 0.3 to 0.4 mg/dl above
baseline.
 Cidofovir therapy must be
discontinued for an increase in serum
creatinine of ≥ 0.5 mg/dL above
baseline or development of ≥ 3+
proteinuria. 65

66.  Renal tubular damage
 Proximal tubular injury – dose dependent
 Proteinuria
 Elevated creatinine levels
 Rash
 Nausea
 Alopecia
 Fever
 Myalgia
66

67.  Systemic adverse effects: Headache ,
Nausea, Pharyngitis
 Local adverse effects: itching, rash
pain, paraesthesias, ulceration
67

68. • Patients receiving agents with nephrotoxic
potential. Such agents must be
discontinued at least seven days prior to
starting therapy
• Patients with hypersensitivity to cidofovir.
• Patients with a history of clinically severe
hypersensitivity to probenecid or other
sulfa-containing medications.
• Pregnancy Cat C
68

69. • Serum creatinine and urine protein
must be monitored within 48 hours
prior to each dose.
• White blood cell counts with differential
should be monitored prior to each
dose.
• In patients with proteinuria, intravenous
hydration should be administered and
the test repeated.
• Intraocular pressure, visual acuity and
ocular symptoms should be monitored
periodically. 69

70.  75 mg/mL for intravenous infusion, is
supplied as a non-preserved solution in
single-use clear glass vials
 375 mg anhydrous cidofovir in a 5 mL
vial in a single-unit carton
 VISTIDE
 Not available in India
 Store at 20-25ºC
 Topical formulation not available
commercially
70

71. • Is a pyrophosphate analogue – trisodium
phosphonoformate.
• It noncompetitively inhibits Viral DNA
polymerase and Reverse transcriptase.
• Exhibits activity against all herpes viruses.
• Used for CMV infection in
immunocompromised.
71

72. • Available as an intravenous
preparation that has poor solubility
and must be administered in an
infusion pump in a dilute solution
over 1-2 hrs.
• Plasma half life – initial phase 4-8
hrs and a terminal component of 88
hrs or longer d/t deposition in bone (
upto 20% of the drug ).
• 80% excreted unmetabolised by
kidney. Dosage reduction in pts with
renal dysfunction 72

73. • Does not require phosphorylation for
its antiviral activity, hence, active
against viruses resistant to acyclovir,
famciclovir or ganciclovir because of
absent / altered kinase activity
• Non competitively blocks pyrophosphate
binding sites on viral polymerases
interference with cleavage of
pyrophosphate from deoxyadenosine
triphosphate – interference with DNA
formation. 73

74.  FDA Approved
 CMV retinitis in AIDS pts.
 Treatment of mucocutaneous acyclovir resistant
HSV infections
 Other Indications
 CMV colitis
 Treatment of CMV polyradiculopathy in patients in
combination with ganciclovir.
 Treatment of ganciclovir resistant CMV infections
74

75. CONDITION DOSAGE ROUTE DURATION
CMV retinitis in
AIDS pt
CMV inf in
transplant
recipients
Induction: 90 mg
/kg 12 hrly
Maintenance: 90
mg/kg to 120mg/kg
/24 hrs
Induction:90
mg/kg12 hrly
IV
IV
IV
14-21 days
Till CD4 count
> 100/ 6 mths of
HAART
15days
Acyclovir
resistant HSV
infection
40 mg/kg 8 hrly / 60
mg / kg 12 hrly
IV 2-3 weeks / till
clinical
resolution
Acyclovir
resistant VZV
infection
40 mg/kg 8 hrly IV 14-26 days
75

76.  Foscarnet sodium is not to be administered as rapid or
bolus intravenous injection as the toxicity of foscarnet
sodium may be increased as a result of excessive
plasma levels.
 Foscarnet sodium is administered by controlled
intravenous infusion, either by using a central venous line
or by using a peripheral vein.
 The standard 24 mg/mL solution may be used with or
without dilution when using a central venous catheter for
infusion.
 When a peripheral vein catheter is used, the 24 mg/mL
solution must be diluted to 12 mg/mL with 5% dextrose in
water or with a 0.9% sodium chloride injection(normal
saline) prior to administration to avoid local irritation of
peripheral veins.
76

77. INVESTIGATIONAL
• Herpes labialis
 3% foscarnet cream applied 8 times a day vs placebo
applied immediately after exposure to UV radiation in UV
radiation induced Herpes labialis
 No diff. - no. of lesions/ duration of lesions
 Significant decrease in mean lesion area in foscarnet
treated pts.
• Genital herpes
 Studies in immunocompetent individuals have not shown
any significant benefit of foscarnet on genital herpes over
placebo.
 Studies in immunocompromised have shown notable
reduction in pain and duration of lesions
77

78. • Renal ( 30%)
 Increased creatinine levels
 Proteinuria
 Nephrogenic diabetes insipidus
 Hypokalemia, Hypocalcemia, hypomagnesemia.
• Headache
• Fatigue
• Fever
• Seizures
• Low white blood cell count, anemia
78

79. • Hydration may reduce the risk of
nephrotoxicity.
• It is recommended that 750 to 1000 mL of
0.9% sodium chloride injection or 5%
dextrose solution should be given prior to
the first infusion of Foscarnet sodium to
establish diuresis.
• With subsequent infusions, 750 to 1000
mL of hydration fluid should be given with
90 to 120 mg/kg of Foscarnet sodium,
and 500 mL with 40 to 60 mg/kg of
Foscarnet sodium.
• Hydration fluid may need to be decreased
if clinically warranted.
79

80. HSV : equivalent to CMV: equivalent to
80 mg/kg /day
total
120 mg /kg/day
total
180 mg/kg/day total
Cr Cl (ml/min/kg) 40mg/kg 12 hrly 40mg/kg 8 hrly 60mg/kg 8 hrly 90mg/kg 12 hrly
>1.4 40mg/kg 12 hrly 40mg/kg 8 hrly 60mg/kg 8hrly 90mg/kg 12 hrly
1.0-1.4 30mg/kg 12 hrly 30mg/kg 12 hrly 45mg/kg 8 hrly 70mg/kg 12hrly
0.8-1.0 20mg/kg 12 hrly 35 mg/kg 8 hrly 50mg/kg 12 hrly 50mg/kg 12hrly
0.6-0.8 35mg/kg 24hrly 25 mg/kg 12 hrly 40 mg/kg 12 hrly 80 mg/kg 24 hrly
0.5-0.6 25 mg/kg 24 hrly 40 mg/kg 24 hrly 60 mg/kg 24 hrly 80 mg/kg 24 hrly
0.4-0.5 20 mg/kg 24 hrly 35 mg/kg 24 hrly 50 mg/kg 24 hrly 50 mg/kg 24 hrly
<0.4 NR NR NR NR
80
NR – not recommended

81. Cr Cl
(ml/min/kg)
90 mg/kg/day ( once
daily)
120mg/kg/day (once daily )
>1.4 90 mg/kg/day 120 mg/kg/day
1.0-1.4 70 mg/kg/day 90 mg/kg/day
0.8-1.0 50 mg/kg/day 65 mg/kg/day
0.6-0.8 80 mg/kg/48hrs 105 mg/kg/48hrs
0.5-0.6 60 mg/kg/48hrs 80 mg/kg/48hrs
0.4-0.5 50 mg/kg/48hrs 65 mg/kg/48hrs
<0.4 NR NR
81

82. • Creatinine clearance :determined at
baseline, 2-3 times per week during
induction therapy and at least every
one to two weeks during maintenance
therapy, with Foscarnet sodium dose
adjusted accordingly.
• Foscarnet sodium should be
discontinued if creatinine clearance
drops below 0.4 mL/min/kg.
• Monitor serum calcium, magnesium,
potassium and phosphorus- 2 to 3
times a week
82

83.  Clinically significant hypersensitivity
to Foscarnet sodium.
 Pregnancy Category C
83

84.  FOSCAVIR : Foscarnet sodium
injection, 24 mg/mL for intravenous
infusion, is supplied in glass bottles.
 Store at 20° to 25°C
 24 mg/mL; 500 mL
 24 mg/mL; 250 mL
 Not available in India
84

85.  Ganciclovir is a synthetic guanine nucleoside
analogue with activity against cytomegalovirus
(CMV).
 It competitively inhibits the binding of
deoxyguanosine triphosphate to DNA polymerase,
thus inhibiting viral DNA synthesis.
 Oral bioavailability-10%
85

86.  Valganciclovir is the L-valyl ester of ganciclovir
that exists as a mixture of two diastereomers.
 After oral administration, both diastereomers are
rapidly converted to ganciclovir by intestinal and
hepatic esterases.
 Oral bioavailability-61%
 With 900mg/dose,peak serum level-
5.61microgram/ml
86

87.  Absorption: Poor absorption after oral admin.
 Distribution: Widely distributed to body tissues
and fluids after IV admin.
 Excretion: Excreted unchanged in the urine
mainly via glomerular filtration and active tubular
secretion. Elimination half-life: 2.5-4.5 hr after IV
admin; increased in renal impairment.
87

88. • Treatment of CMV retinitis in patients with acquired
immunodeficiency syndrome (AIDS).
 Induction dose - 5mg/kg IV 12 hrly X10-21 days.
 Maintenance dose-5mg/kg IV 24 hrly until CD4 count> 100 OR
after 6 month of HAART
 OR
Valganciclovir 900 mg twice a day orally X 21 days &
maintenance dose- 900 mg OD until CD4 count >100 after 6
month of HAART
• Prevention of CMV infection in bone marrow transplant
patient.
 Induction dose -5mg/kg 12 hourly X 14-21 days
 Maintenance dose -5mg/kg /day IV for 100-120 days post
transplant
88

89. Dose
Prevention of CMV
infection in heart
transplant pts.
900mg once a day within
10 days of transplant to
100 days of post
transplant
Prevention of CMV
infection in kidney
transplant pts.
900mg once a day within
10 days of transplant to
200 days of post
transplant
89

90. 90

91.  Hypersensitivity to valganciclovir or ganciclovir
 Pregnancy cat. C
91

92.  Hematologic effects:
o Severe leukopenia, neutropenia, anemia,
thrombocytopenia, pancytopenia, bone marrow
depression, and aplastic anemia.
o Do not administer if absolute neutrophil count is <
500 cells/μL, platelet count is < 25,000/μL, or
hemoglobin is < 8 g/dL. Use with caution in
preexisting cytopenias and when receiving
myelosuppressive drugs or irradiation.
o Monitor with frequent testing of platelet and
complete blood counts
 Impairment of fertility:
o Ganciclovir may cause temporary or permanent
inhibition of spermatogenesis .
92

93.  Teratogenesis and mutagenesis:
o Ganciclovir is potentially teratogenic and mutagenic.
Women of childbearing potential should use
contraception during and following treatment ( 30
days) and men should practice barrier contraception
during and following treatment (90 days).
 Acute renal failure:
o Acute renal failure may occur in elderly patients
(with or without reduced renal function),
o patients who receive concomitant nephrotoxic
drugs,
o or inadequately hydrated patients.
o Use with caution in elderly patients or those taking
nephrotoxic drugs, reduce dosage in patients with
renal impairment, and monitor renal function
93

94.  diarrhea, nausea and vomiting
 pyrexia, tremor
 neutropenia, anemia,
thrombocytopenia,
 graft rejection
94

95. • VALCYTE (Valganciclovir ) tab 450 mg x 60's (62400
INR); Roche
• GANGUARD cap 250mg x10’s(1218.30 INR)
cap 500mg x10’s(2205.10 INR)
• CYMEVENE cap 250 mg x 10's
cap500 mg x 10's
• CYMEVENE vial 500 mg x 1's (1872 INR); Roche
• CYTOGAN vial500 mg x 1's; AHPL
• GAVIR vial500 mg x 1's; United Biotech
• VITRASERT(OCCULAR IMPLANT) ;Baush&Lombs
95

96. ANTIVIRA
L DRUG
HSV1 HSV2 VZV
CMV MAIN
TARGET ORG.
ACY,
VALACY
+++ +++ ++ - HSV1,2, VZV
CIDOFOVI
R
+ + ++ +++ CMV, resistant
HSV
FAMCI +++ +++ ++ - HSV1,2, VZV
FOSCARN
ET
++ ++ + ++ CMV, resistant
HSV, VZV
GANCICLO
VIR/
VALGAN
+ + + +++ CMV
96
HV- Herpes viruses

97. Thank you!