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Disease State Presentation: Herpes Simplex Virus

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

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

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  • 1. DiseaseHERPES 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. HerpesBACKGROUND 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 SimplexPRESENTATIONS 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. HerpesDIAGNOSIS 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 TherapyRecommendations 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®) FormulationsFormulation Unit Count Estimated PriceGeneric 200mg Capsules 30 $10 - 20Generic 200mg/5mL Oral 473 mL $10 - 20SuspensionGeneric 400mg Tablets 60 tabs $20 - 40Generic 800mg Tablets 30 tabs $20 - 40Brand 200mg Capsules 30 caps $20 - 40Brand 200mg/5mL Oral Suspension 473 mL $100 - 150Brand 400mg Tablets 60 tabs $100 - 150Brand 800mg Tablets 30 tabs $100 - 150Generic 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 infectionFormulation Unit Count Estimated PriceBrand 5% Cream 1 tube, 2 grams $100Brand 5% Cream 1 tube, 5 grams $180Brand 5% Ointment 1 tube, 15 grams $60-100Brand 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®) FormulationsFormulation Unit Count Estimated PriceGeneric 125mg Tablets 30 tabs $160Generic 250mg Tablets 30 tabs $170Generic 500mg Tablets 30 tabs $330Brand 125mg Tablets 30 tabs $200Brand 250mg Tablets 30 tabs $216Brand 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®) FormulationsFormulation Unit Count Estimated PriceGeneric 1g Tablets 30 tabs $350Generic 500mg Tablets 30 tabs $170Brand 1g Tablets 30 tabs $370Brand 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’
  • 42. 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 .