Valacyclovir is an anti viral drug .This presetation contain about herpes disease and its treatment with valacyclovir .Usefull for doctor ,nurses ,& pharmacist

1. DR SAURAV DEKA
MEDICAL ADVISOR –
ZYDUS MEDICAL SERVICE INTERNATIONAL DIVISION
Email: hisaurav2007@gmail.com

2. CONTENTS
• INTRODUCTION TO VIRUS
• INTRODUCTION TO ANTIVIRALS
• HUMAN HERPES INFECTION
• ANTI VIRAL DRUGS
• VALACYCLOVIR
-Indication
-Doses
- Mechanism of Action
- ADME
-Side effects
- Questions

3. VIRUSES, WHAT ARE THEY?
• Viruses are all parasites of the living
• They cannot make anything on their
own, they use the cell’s materials to
build themselves
• THERE IS TWO TYPE OF VIRUSES
– DNA virus
(adenovirus, cytomegalovirus, Epst
ein-Barr, Herpes, Varicella etc )
– RNA virus
(hepatitis, flu, measles/mumps, RSV,
polio, rhinovirus, HIV, rabies, rubella
etc )

4. VIRAL REPLICATION

5. Human Herpes Viruses
1.HSV-1 and HSV-2
ANVIRO
2.Varicella-zoster virus (VZV)
3.Cytomegalovirus (CMV)
4.HHV-6 and HHV-7
5.Epstein-Barr Virus (EBV)
6.Kaposi’s sarcoma-associated herpesvirus
(KSHV,HHV-8)

6. Anti virals, why?
• Vaccines are effective at prevention but what not for
the patient that is already infected
• Viruses can be very swift and deadly and a quick
method of curing a patient is needed
• The market is huge and a remedy would bring about
solutions to viral infections such as: Influenza, HIV,
Herpes, Hepatitis B, Smallpox, Ebola, Rabies, etc.

7. SOME BLOCK BUSTER ANTI VIRALS
Tamiflu-
• Recently sold to 40 countries to
battle avian flu
• Prevents the mature viruses
from leaving the cell
• It is a neuraminidase
inhibitor, it works on both
influenza A and B
• Neuraminidase is an enzyme
found on the virus which
cleaves sialic acid from cell
membrane, leading to a more
effective release of viruses.
mechanism
27 MAR 2007 Antiviral Drugs: An Overview

8. SOME BLOCK BUSTER ANTI
VIRALS
Aciclovir-
• A widely used antiviral with
main implications in the
treatment of herpes
• Seen as a “new age” in
antiviral therapy, Gertrude
Elion, its creator, was given
the Nobel prize for
medicine in 1988
• It is a nucleoside analogue
and prevents viral
replication in infected cells
Antiviral Drugs: An Overview

9. PHARMACOLOGY of ANTIVIRALS

10. Chemotherapy for HSV
O
O
N
N HN
HN
N N
H2N
N
H2N N
H2N O
HO O
O
O
Acyclovir (Zovirax) Valacyclovir (Valacyclovir),
O O
N N
HN HN
N N N
H2N H2N N
HO
AcO
OH
OAc
pencyclovir Famcyclovir (Famvir),

11. Antiviral Chemotherapy for HSV
• There are several prescription antiviral
medications for controlling herpes outbreaks,
include acyclovir (Zovirax), valacyclovir
(Valacyclovir), famcyclovir (Famvir), and
pencyclovir.
• Acyclovir was the original and prototypical
member of this class
• Valacyclovir and famcyclovir are prodrugs of
acyclovir and pencyclovir respectively, with
improved oral bioavailability.

12. Mechanism of Action of Anti virals to treat
HSV
• Both acyclovir and pencyclovir work by
interfering with viral replication, effectively
slowing the replication rate of the virus, and
providing a greater opportunity for the immune
response to intervene.
• All drugs in this class depend on the activity of
the viral thymidine kinase to convert the drug to
a monophosphate form and subsequently
interfere with viral DNA replication.

13. Human Herpes Viruses
1.HSV-1 and HSV-2
2.Varicella-zoster virus (VZV)
3.Cytomegalovirus (CMV)
4.HHV-6 and HHV-7
5.Epstein-Barr Virus (EBV)
6.Kaposi’s sarcoma-associated herpesvirus
(KSHV,HHV-8)

14. Herpes simplex virus
 Ubiquitous virus that infects greater than 75% of
the adult population (HSV-1) and to varying
degrees in the case of HSV-2, depending on the
population studied.
 Manifestations depend on anatomic site
involved, age, immune status of the host like
Herpes labialis ,Genital herpes etc.
 About one in five people in the United States over age
12 (approximately 45 million individuals) are infected
with HSV-2, the virus that causes genital herpes.

15. Herpes Labials or cold soar

16. Genital Herpes
• Lesions:
vesicles, pustules, erythe
matous ulcers
• Can be caused by HSV-1
&2
• Recurrence rate higher
with HSV-2 infection
• Trigeminal ganglia &
sacral ganglia- most
common sites of HSV-1
and HSV-2 latency

17. How severe an infection?
• HSV is a lifelong illness
• But HSV-2 usually produces only mild symptoms or
signs or no symptoms at all. However, HSV-2 can cause
recurrent painful genital sores in many adults, and HSV-
2 infection can be severe in people with suppressed
immune systems.
• Another factor is how long a person has had the
infection. It seems to decrease in severity over
time, for reasons which are unclear.

18. TREATMENT OF HERPES SIMPLEX ( COLD SORE
,GENITAL )

19. Human Herpes Viruses
1.HSV-1 and HSV-2
2.Varicella-zoster virus (VZV)
3.Cytomegalovirus (CMV)
4.HHV-6 and HHV-7
5.Epstein-Barr Virus (EBV)
6.Kaposi’s sarcoma-associated herpesvirus
(KSHV,HHV-8)

20. VARICELLA ZOSTER VIRUS (VZV)
VZV causes two major syndromes
1. VARICELLA : CHICKEN POX
2. ZOSTER : SHINGLES

21. Chickenpox (Varicella )
• Childhood disease
• Highly contagious: pt infectious 48hrs prior to
rash.
• IP: 10-21 days
• Fever, malaise, skin lesions:
maculopapules, vesicles, pustules, scabs in
various stages of evolution
• Early lesions “dew drop on rose petal”
• Diagnosis: clinical, VZV DNA PCR, Tzanck
smear demonstrating multinucleate giant
cells, Direct immuno fluorescence
• Childhood Vaccination

22. ETIOLOGY OF SHINGLES (ZOSTER )
• Primary infection occurs when the virus comes into contact
with the mucosa of the respiratory tract or conjunctiva
• From these sites, viral multiplication occurs a haematogenous
spread follows
• VZV persists in the sensory ganglia of the cranial and spinal
dorsal root ganglia after varicella resolves
• 20 % Varicella (Chicken pox) cases in later life
develop shingles

23. Clinical spectrum of Shingles
1. Typical zoster presents as a painful macuopapular eruption
distributed along a dermatome ( area)
2. Recurrent zoster is exceedingly rare in the immunocompetent.
May involve more than one dermatome (area)
3. Chronic disseminated zoster may present as verrucous or
ulcerative lesions
4. Zoster ophthalmicus :Zoster involving the ophthalmic branch of
the trigeminal nerve .
5. visceral dissemination may also occur, resulting in life
threatening infections of the liver, lungs and CNS

24. SHINGLES (Zoster)
•
Adapted from: gb.udn.com

25. HZ: Involvement of tip of nose is classic indicator
of ocular involvement (Hutchinson’s sign)

26. Diagnosis of herpes zoster
• Typical zoster is diagnosed clinically.
• Atypical or disseminated forms of zoster may require
laboratory confirmation by viral culture, Tzanck smear or DFA.
PCR may be utilised for the diagnosis of CNS infection or
pneumonitis

27. ZOSTER IS VERY PAINFUL
There are three different ways to evaluating pain
1.Acute Pain :Pain at presentation that can be
quantified overthe first 30days
2.PHN (post herpetic neuralgia) : Defined by the
USFDA as “pain That has not resolved 30 days
after disease onset";although an alternative
definition is pain that persists after healing or
Pain 90days after rash onset;
3. Zoster-Associated Pain (ZAP) :where by pain is
viewed from the time of acute zoster until its
complete resolution.

28. Management of Zoster
GENERAL :Rest and analgesics are sufficient for mild attacks of
shingles. Soothing anti-septic applications may help and
secondary bacterial infections will require antibiotic therapy.
SPECIFIC : Antivirals , for 7-10 days until lession crusted

29. CMV disease
• β Herpes virus dsDNA  Pneumonitis
 Bone marrow transplant
• Spread by repeated prolonged
 Colitis
exposure
 AIDS, solid organ
• CMV present in breast transplantation
milk, saliva, feces, urine, semen,  Retinitis
cervical secretions  AIDS
• Daycare centers  Hepatitis
• Once infected person carries  SOT
CMV for life.  Nephritis
 Kidney transplantation
• Reactivation syndromes: T cell
 Mononucleosis:
mediated immunity
 Congenital infection:
compromised IUGR, microcephaly, chorioretinitis

30. CMV treatment Internationally
DRUG DOSE
1. Ganciclovir IV 5 mg/kg bid x 14–21 d;
then 5 mg/kg per
day as maintenance dose
2. Valgancyclovir ,oral 900 mg bid x 21 d;
then 900 mg/d as maintenance dose
3.Foscarnet IV 60 mg/kg q8h x 14–21 d;
then 90–120 mg/kg per
day as maintenance
dose
4 .Cidovir IV 5 mg/kg once weekly x 2
weeks, then once every
other week; given with
5.Fomivirsen 330 mg on days 1 and 15
followed by 330 mg
monthly as maintenance

31. Valacyclovir is approved for CMV in South
Africa

33. What is ANVIRO ?
• It is Valacyclovir generic of Zelitrex
• It is patented by Glaxo-South Kline (VALTREX
,Zelitrex)
• It is used to treat Shingles (Herpes-zoster) and genital
herpes
• It does not cure the herpes virus, but it reduces pain
and itching, helps sores heal, and reduce the risk of new
sores forming.
• There is a generic on the market as on 2010. Created by
Tebrau which is under the Indian company Ranbaxy.

34. INDICATION
1) FDA Approved Indications
a) Genital herpes simplex, Initial and recurrent episodes
b) Herpes labialis
c) Herpes zoster, Shingles
d) HIV infection - Recurrent genital herpes simplex, Suppression
e) Recurrent genital herpes simplex, Suppression and transmission
reduction
f) Varicella
2) Non-FDA Approved Indications
a) Genital herpes simplex, Initial and recurrent episodes - HIV infection
b) Herpes labialis - HIV infection
c) Herpes zoster, Shingles - HIV infection
•
•

35. Variation in indication USFDA vs MCC

36. DOSES In HSV & VZV

37. MOA of VALACYCLOVIR
VALACYCLOVIR is rapidly converted to acyclovir is highly selective due
to its affinity for the enzyme thymidine kinase (TK) encoded by HSV
and VZV.
This viral enzyme converts acyclovir into acyclovir monophosphate, a
nucleotide analogue. The monophosphate is further converted into
diphosphate by cellular guanylate kinase and into triphosphate by a
number of cellular enzymes.
This process results in blocking the replication of the herpes viral DNA.

38. PHARMACOKINETICS
ABSORBTION (active acyclovir):Oral bioavailability of valacyclovir
is significantly greater than that of acyclovir comparable
54.5%
DISTRIBUTION : Highly protein bind cross blood brain & placental
barrier
METABOLISM :Valacyclovir is a prodrug that is rapidly converted
to acyclovir (active metabolite) by first pass intestinal or
hepatic metabolism
Elimination half life : 2.5 to 3.3 hours, healthy volunteers
ELIMINATION : Renal : 46-47 %
Feces : 47%

39. Side Effects
• Headache
• Upset stomach, nausea
• Diarrhea or loose stools
• Constipation
• Rash
• Itching
• Confusion
• Yellowness of the skin or eyes
• Fever
• Blood in urine

40. SOME COMPARATIVE STUDY
Genital Herpes & Herpes Zoster :
Valacyclovir better than acyclovir
Efficacy similar to famcyclovir
Cyto Megalo Virus :
Valacyclovir better than acyclovir gancyclovir
* Egan J, Carroll K, Yonan N, et al: Valacyclovir prevention of cytomegalovirus reactivation after heart transplantation: A randomized trial. J Heart Lung Transplant 2002;
21:460-466.
* Ljungman P, Camara R, & Milpied N: Randomized study of valacyclovir as prophylaxis against cytomegalovirus reactivation in recipients of allogeneic bone marrow
transplants. Blood 2002; 99:3050-3056

41. IN HIV it is better than Acyclovir
The Journal of Infectious Diseases 2011;204:1912–7
Dose : valacyclovir 1.5g vs acyclovir 400mg ,both twice daily for
12weeks

42. SOME COMPARATIVE STUDY
Table 1. Recommended
Regimens for Treatment of
Dosage
Herpes Simplex Virus in HIV-
1-Infected Individuals
Drug Episodic Therapy Suppressive Therapy
400 mg orally 3 times per day 400-800 mg orally 2-3 times
Acyclovir
for 5-10 days per day
500 mg orally 2 times per day
Famciclovir 500 mg orally 2 times per day
for 5-10 days
1,000 mg orally 2 times per
Valacyclovir 500 mg orally 2 times per day
day for 5-10 days
Source: Centers for Disease Control and Prevention. Sexually Transmitted Diseases
Treatment Guidelines, 2006. Morb Mortal Wkly Rep 2006;55:1-94.