Presented during Community Pharmacy Rotation at Walgreens in Oakland Park, Florida.

1. Disease
HERPES SIMPLEX VIRUS State
Presentation
Joy A. Awoniyi
Pharm.D Candidate 2012
Florida A&M University
October 21, 2011
Community Pharmacy Rotation
Preceptor: Dr. Kayon Samuels-Dennis

2. OBJECTIVES
THE PURPOSE OF THIS PRESENTATION IS TO:
 D e f i ne h e r p e s s i m pl e x v i r us
 P r o v i d e a b a c k g r o und r e g a r d i ng t h e e p i de mi ol o gy a n d m e t h o d s o f
t r a n s m i ssi on o f t h e v i r us
 R e v i e w t h e c o m p l ic a ti o ns a s s o c i a t e d w i t h t h e d i s e a se
 D i f f e r e n ti a t e b e t w e e n t h e t w o t y p e s o f h e r p e s s i m pl e x v i r use s
 H i g hl i g ht t h e s i g ns a n d s y m p to m s a s s o c i a t e d w i t h t h e d i a g no si s o f t h e
d i se a se
 D i s ti ng ui sh H S V f r o m o t h e r d i s e a s e s t a t e s w i t h s i m i la r c l i ni ca l p r e s e n t a ti on s
 P r o v i d e a n o v e rv i e w o f t h e a v a i l a b l e p h a r m a c ol ogi c a l u s e d t o m a n a g e H S V
 E x p l a i n m o d e s o f p r e v e nti on o f t h e s p r e a d a n d a c q ui si ti o n o f t h e v i r us
 E m p ha si z e t h e r o l e o f t h e p h a r m a ci s t i n t h e t r e a t m e n t o f p a t i en t s w i t h H S V

3. Herpes
BACKGROUND Simplex
Virus

4. DEFINITION
 Herpes simplex viruses are host -adapted pathogens that
cause a wide variety of disease states
 Double-stranded DNA viruses characterized by
 Neurovirulence – the ability to invade the nervous system
 Latency
 Reactivation – which can be induced by various stimuli such
as fever or emotional stress

5. EPIDEMIOLOGY
 By age 30, 50% of those in a high socioeconomic status
an 80% in a lower socioeconomic status are seropositive
for HSV-1
 Lifetime seroprevalence of HSV-2 can be anywhere
between 20 – 80%
 HSV-2 is more common in women (25%) than in men
(17%)
 In the United States, HSV-2 is more prevalent in blacks
(45%) as compared to Mexican -Americans (22%) and
Whites (17%)

6. TRANSMISSION
 Humans are the only
natural reservoirs
 Transmission occurs by
close personal contact
 Infection occurs by
way of inoculation of
the virus into
susceptible mucosal
surfaces
 The virus is inactivated
at room temperature
and by drying

7. TYPES OF HERPES SIMPLEX VIRUS
HSV-1 HSV-2
 Traditionally associated  Traditionally associated
with orofacial disease with genital disease
 Reactivates more  Reactivates 8-10 times
frequently in the oral more frequently in the
region genital region than the
orolabial
 Usually acquired in  Presence may be an
childhood indirect measure of sexual
activity, in some cases
 Transmitted chiefly by
contact with infected  Transmitted sexually or
saliva from a mothers genital
tract infection to her
newborn

8. COMPLICATIONS
 Bacterial and fungal super -  CNS I nvolvement
infections  Aseptic Meningitis
 Ganglionitis and myelitis
 Ocular infections  Herpes Simplex Encephalitis
(70% mortality rate untreated)
 Conjunctivitis
 HSV-2 is more commonly
 HSV is the leading infectious associated with CNS infection
cause of blindness in the in newborns, HSV-1 in adults
United States
 Pregnancy complications
 Skin Infections  Neonatal Infection leading to
 Eczema Herpeticum uterine growth retardation and
 Herpetic Whitlow (involvement premature births
of the fingers)
 Herpes gladiatorum: scattered  Neonatal disease
HSV 1 lesions observed in
wrestlers  Risk of mother to child
transmission is 50%
 Visceral I nfections
 I ncreased risk of HIV
infection

9. CLINICAL Herpes
Simplex
PRESENTATIONS Virus

10. HERPES SIMPLEX VIRUS TYPE 1
Herpes Labialis
 Most common manifestation of
recurrent HSV-1 infection
 May last up to 5 days and occur in
most patients less than twice per year
 Sign
 Erythematous papules rapidly developing
into tiny vesicles that eventually ulcerate
 Symptoms
 Pain, burning and tingling at the site prior
to papule formation

11. HERPES SIMPLEX VIRUS TYPE 1
Acute Herpetic Gingivostomatits
 Primarily seen in younger patients (6
months – 5 years) but may occur
more acutely and less severely in
adults
 Abrupt onset, lasting 5 – 7 days
 Signs
 High temperatures between 102 and 104 °
 Gingivitis is the most striking feature
 Vesicular lesions on the oral mucosa,
tongue, and lips
 Symptoms
 Anorexia and listlessness

12. HERPES SIMPLEX VIRUS TYPE 1
Acute Herpetic Pharyngotonsilitis
 Pharyngotonsilitis is seen more often
in adults
 Signs
 Oral and labial lesions occur in less than
10% of patients
 Ruptured vesicles may rupture and form
ulcerative lesions with gray exudates n
the tonsils and posterior pharynx
 Fever
 Symptoms
 Malaise
 Headache
 Sore throat

13. PRIMARY (FIRST EPISODE)
GENITAL HERPES
 May be caused by either type of HSV
 Clinical features are indistinguishable
 Recurrence is more common with HSV-2
 Incubation period is anywhere between 1 day to 3 weeks
 Symptoms
 Systemic: Fever, headache, malaise an myalgia
 Local: Pain, itching, dysuria, vaginal and urethral discharge,
tender lymphadenopathy
 Severe and prolonged manifestations
 May be asymptomatic
 Ulcerative lesions persist anywhere from 4 to 15 days. In
75% of patients, new lesions will form in 4 -10 days

14. PRIMARY GENITAL HERPES
Men
 Vesicles appear in the glans
penis and prepuce, or shaft of
the penis
 May also appear on the scrotum,
thighs, and buttocks
 30 – 40% of men may experience
herpetic urethritis which presents
as severe dysuria and mucoid
discharge
 Herpetic proctitis involves the
perianal area and rectum and is
more commonly involved in
those who engage in anal
intercourse

15. PRIMARY GENITAL HERPES
Women
 Vesicles appear on the external
genitalia, labia minora and
majora, vaginal vestibule, and
introitus
 70 – 90% of women experience
cervical involvement, which may
be ulcerative or necrotic to the
mucosa
 Cervicitis is the sole manifestation in
some women
 Dysuria may occur
 May cause urinary retention
 May be associated with urethritis, which
is seen more often with the HSV Type 1

16. RECURRENT GENITAL HERPES
 90% of patients are reactivated with genital herpes within
the first 12 months
 HSV-2 is reactivated more commonly, with 60%of patients
experiencing recurrences within the first year
 Symptoms
 Tenderness, pain, and burning at the site of eruption lasting from
2 hours to 2 days
 Fever is uncommon
 More severe in women than men
 The frequency and severity of recurrence decreases with
time
 Lesions generally heal within 8 to 10 days in women, and
between 7 and 10 days for men
 Infection lasts may last over 30 days in immunocompromised
patients

17. SUBCLINICAL GENITAL HERPES
 Most primary HSV infections are asymptomatic
 70-80% of seropositive individuals have no known history of
genital herpes

18. Herpes
DIAGNOSIS Simplex
Virus

19. LABORATORY STUDIES
The criteria for standard diagnosis includes isolation of
the virus in tissue culture
 Immunofluorescent  Polymerase Chain
staining: Distinguishes Reactions: Detects HSV
between types of herpes DNA in clinical specimens
simples virus as well as non -  Can also detect
herpes viruses asymptomatic viral shedding
 Tzank Smears: Assists in the  Direct Fluorescent Antigen :
diagnosis of cutaneous Staining with fluorescent
herpes virus infections, but antibodies may distinguish
does not distinguish between types
between types

20. DIFFERENTIAL DIAGNOSES
 Candidiasis: Fungal infection
 Chancroid: STD and Cofactor in HIV transmission
 Hand-foot-and-mouth Disease: transmitted by the fecal -
oral route
 Herpes Zoster (Shingles): Benign course
 Syphilis: STD with nonspecific manifestations

21. PHARMACOLOGICAL Herpes
Simplex
TREATMENTS Virus

22. MEDICATION THERAPY GOALS
 Reduce morbidity
 Prevent complications

23. HSV THERAPY
 Antiviral Agents
 These agents are nucleoside analogs that are phosphorylated
by thymidine kinase to form a nucleoside triphosphate which
inhibits HSV polymerase
 Mechanism of action:
 Interferes with DNA Polymerase to inhibit DNA replication by
way of chain termination
 Only oral agents are recommended for the
treatment of genital herpes, while both
prescription and over-the counter agents may
be used to treat cold sores

24. RECOMMENDED REGIMENS FOR
GENITAL HERPES
First Episode Suppressive Therapy
Recommendations from the Department of Health and Human Services Centers for Disease Control and Prevention
Sexually Transmitted Diseases Guidelines, 2010.

25. ACYCLOVIR (ZOVIRAX®)
 Used for both types of HSV
 Side effects
 Malaise
 Nausea, vomiting
 Pruritus
 Acute Renal failure
 Pregnancy Category B
 Avoid use with other
nephrotoxic drugs as renal
failure resulting in death
has occurred

26. ACYCLOVIR (ZOVIRAX®)
Adult Dosing Pediatric Dosing
 Initial Treatment:  Neonatal HSV
 200mg PO Q4H 5 times daily
x 7-10 days  20mg/kg/day div Q8H
 400mg PO TID x 5-10 days IV x 14-21 days
 Recurrence Treatment
 200mg PO Q4H 5times daily  HSV Encephalitis
x 5 days
 Initiate at the earliest sign or  3 months -12 yrs:
symptom of recurrence 20mg/kg Q8H x 10 days
 Chronic Suppression  12 and older: 10-
 400mg PO BID up to 12 15mg/kg IV Q8H x 14-12
months days
 200mg 3-5 times daily for up
to 12 months

27. ACYCLOVIR (ZOVIRAX®)
 Formulations
Formulation Unit Count Estimated Price
Generic 200mg Capsules 30 $10 - 20
Generic 200mg/5mL Oral 473 mL $10 - 20
Suspension
Generic 400mg Tablets 60 tabs $20 - 40
Generic 800mg Tablets 30 tabs $20 - 40
Brand 200mg Capsules 30 caps $20 - 40
Brand 200mg/5mL Oral Suspension 473 mL $100 - 150
Brand 400mg Tablets 60 tabs $100 - 150
Brand 800mg Tablets 30 tabs $100 - 150
Generic Powder for injection 500mg and 1g vials --------------------
Generic IV solution 50mg/mL multiple --------------------

28. ACYCLOVIR TOPICAL
(ZOVIRAX® OINTMENT OR CREAM)
 IMPORTANT NOTE: This formulation has no clinical
benefit for recurrent genital herpes and is ineffective
against herpes labialis
 Recommended Adult Dose for INITIAL OCCURRENCE:
 Apply Q3H 6 times daily x 7 days
 Start therapy at the earliest sign or symptom of infection
Formulation Unit Count Estimated Price
Brand 5% Cream 1 tube, 2 grams $100
Brand 5% Cream 1 tube, 5 grams $180
Brand 5% Ointment 1 tube, 15 grams $60-100
Brand 5% Ointment 1 tube, 3 grams $20-40

29. ACYCLOVIR AND HYDROCORTISONE
(XERESE®)
 Used to treat herpes labialis in patients over 12 years
 Recommended Adult Dose:
 Apply 5 times daily x 5 days
 Start therapy at the earliest sign or symptom of infection
 May cause pigment changes

30. FAMCICLOVIR (FAMVIR®)
 Used for both types of HSV
 Dose renally when CrCl is less
than 60mL/min due to risk of
acute renal failure
 Side effects
 Headache
 Nausea
 Fatigue
 Fever
 Pregnancy Category B
 Pro-drug that is
biotransformed into its active
metabolite, Penciclovir

31. FAMCICLOVIR (FAMVIR®)
Adult Dosing Pediatric Dosing
 Recurrent Herpes Labialis  Safety and efficacy
 1500mg PO once has not been
established in this
 Primary Genital HSV population, but the
 250mg PO TID x 5-10 days medication is used off-
 Off-label indication label in adolescents
 Recurrent Genital HSV
 1000mg PO BID x 1 day
 Primary Genital HSV
 HIV Patients: 500mg PO BID  250 mg PO TID x 7-10days
x 7days
 Chronic Suppression
 Chronic Suppression  125-250 mg PO BID up to
 250mg PO BID up to 12 12 months
months

32. FAMCICLOVIR (FAMVIR®)
 Formulations
Formulation Unit Count Estimated Price
Generic 125mg Tablets 30 tabs $160
Generic 250mg Tablets 30 tabs $170
Generic 500mg Tablets 30 tabs $330
Brand 125mg Tablets 30 tabs $200
Brand 250mg Tablets 30 tabs $216
Brand 500mg Tablets 30 tabs $450

33. PENCICLOVIR (DENAVIR®)
 Used topically for  Adult Dosing
Herpes Labialis  Apply Q2H x 4 days
 No pediatric dosing
 Side effects information
 Headache
available
 Taste changes
 Erythema
 Pruritus
Formulation Unit Estimated Price
 Pregnancy Count
Category B Brand name 1 tube $100
1% cream (1.5g)

34. VALACYCLOVIR (VALTREX®)
 Used for both types of HSV
 Provides an advantage as it reduces the
risk of heterosexual transmission of
genital herpes to susceptible partners
when used as suppressive therapy
 M ore expensive pro -drug of A cyclovir,
with more convenient dosing
 Side effects
 Abdominal pain
 Headache
 Nausea
 Depression
 Pregnancy Category B
 Renal dosing is required when creatinine
cl earance is l ess than 50mL/min

35. VALACYCLOVIR(VALTREX®)
Adult Dosing Pediatric Dosing
 Recurrent Herpes  Safety and efficacy
Labialis
 2 PO Q12H x 1 day has not been
established in this
 Primary Genital HSV population
 1g PO BID x 10days
 Recurrent Genital HSV
 500mg PO BID x 3 days
 Chronic Suppression
 1 g PO Daily
 500mg PO BID if HIV-
infected

36. VALACYCLOVIR (VALTREX®)
 Formulations
Formulation Unit Count Estimated Price
Generic 1g Tablets 30 tabs $350
Generic 500mg Tablets 30 tabs $170
Brand 1g Tablets 30 tabs $370
Brand 500 mg Tablets 30 tabs $240

37. DOCOSANOL (ABREVA®)
 Available over the counter for the treatment of herpes
labialis
 Mechanism of Action:
 Inhibits the fusion of the herpes simplex virus envelope with host
cell plasma membranes. This results in the inhibition of viral entry
into cells and subsequent viral replication
 Side effects
 HSV development outside the treatment area
 Headache
 Application site reactions
 Recommended dosing
 Apply topically to cover all lesions 5 times daily until healed
(Maximum of 10 days)

38. TOPICAL OVER-THE-COUNTER AGENTS
FOR HERPES LABIALIS
The following medications may be recommended over the
counter for the treatment of cold sores in individuals older than 2
years and are applied as needed for a maximum of 4 days
 Anbesol Cold Sore  Orajel Cold Sore Swabs
 Benzocaine, Camphor,  Benzocaine Topical
allantoin, Petrolatum
Topical
 Orajel Cold Sore Brush or
 Neosporin LT Lip Multi-Action cold sore
treatment  Benzocaine, allatoin,
dimethicone, petrolatum
 Pramoxine/ allantoin topical
topical
 Zilactin Cold Sore Gel or
 Orajel Overnight Cold Solution
Sore Patch  Benzoyl Alcohol Topical
 Dyclonine Topical

39. PREVENTION AND Herpes
Simplex
FOLLOW-UP Virus

40. PREVENTION
 Latex condoms are recommended to minimize exposure
to genital herpes infections
 Ulcers may occur outside of the condom, and transmission is
still possible
 Herpetic whitlow can be avoided by the use of latex
gloves when inserting the hand into an oral cavity
 Daily antiviral therapy can be given to reduce episodes
of asymptomatic viral shedding

41. PHARMACISTS ROLE
 Compliance
 Encourage adherence to medication
regimens to decrease transmissions
 Check to see if patients are keeping
physician appointments
 Identify barriers to medication
adherence
 Counseling
 Give unbiased clinical advise on OTC
treatments
 Educate patients on the modes of
transmission
 Encourage patients with genital
herpes to inform sexual partners
regarding their diagnosis’

43. REFERENCES
 C e n t e r s f o r D i s e as e C o n t r o l an d P r e v e n ti o n. “ G e n i t al HS V I n f e c tio n s”.
M M W R 2 0 1 0 ;5 9 (No . R R - 1 2 ): 2 0 - 2 4 .
 K i m b e rl i n D Q , R o u s e D J . C l i n i cal P r ac t i c e . G e n i t al He r p e s . N E n g l J
Me d . M ay 6 2 0 0 4 ;3 5 0 (1 9 ):1 9 7 0 - 7 7 .
 Nag o t N, O u e d r ao go A , F o u l o n g n e V, e t al . R e d u c t i o n o f HI V - 1 R NA
l e v el s w i t h t h e r ap y t o s u p p r e s s h e r p e s s i m p l e x v i r us . N E n g l J Me d .
2 0 0 7 ;3 5 6 (8 ):7 9 0 - 9 9 .
 A r d ui n o P G , P o r t e r S R . O r al an d p e r i o r al h e r p e s s i m p l e x v i r us t y p e 1
(HS V - 1 ) i n f e c t i o n : r e v i e w o f i t s m an ag e m e n t .
 S al v agg i a M R . “ He r p e s S i m p l e x ”. M e d s c ap e R e f e r e n c e . A v ai l abl e at :
h t t p ://e m e dici n e .m e dsc ap e.c o m /articl e / 2 1 8 5 8 0 . A c c e s s e d o n 1 7 O c t
2 0 1 1 . L as t u p d at e d 3 D e c 2 0 1 0 .
 “ A n ti v iral ag e n t s f o r t h e t r e at m e n t o f c o m m o n h e r p e t i c i n f e c t i on s i n
i m m u n o c o m p e te n t p at i e n t s”. P h ar m ac i s t’s L e t t e r 2 0 0 2 ; 1 8 (1 0 ):1 8 1 0 0 7 .