valacyclovir training south africa dr deka
DESCRIPTION
Valacyclovir is an anti viral drug .This presetation contain about herpes disease and its treatment with valacyclovir .Usefull for doctor ,nurses ,& pharmacistTRANSCRIPT
VALACYCLOVIR mail me if you downloaded this anti virus
DR SAURAV DEKA MEDICAL ADVISOR –ZYDUS MEDICAL SERVICE INTERNATIONAL DIVISIONEmail: [email protected]
CONTENTS
• INTRODUCTION TO VIRUS• INTRODUCTION TO ANTIVIRALS• HUMAN HERPES INFECTION• ANTI VIRAL DRUGS • VALACYCLOVIR -Indication -Doses - Mechanism of Action - ADME -Side effects - Questions
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, Epstein-Barr, Herpes, Varicella etc )
– RNA virus (hepatitis, flu, measles/mumps, RSV, polio, rhinovirus, HIV, rabies, rubella etc )
VIRAL REPLICATION
Human Herpes Viruses
1.HSV-1 and HSV-22.Varicella-zoster virus (VZV)3.Cytomegalovirus (CMV)4.HHV-6 and HHV-75.Epstein-Barr Virus (EBV)6.Kaposi’s sarcoma-associated herpesvirus
(KSHV,HHV-8)
ANVIRO
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.
27 MAR 2007 Antiviral Drugs: An Overview
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
Antiviral Drugs: An Overview
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
PHARMACOLOGY of ANTIVIRALS
Chemotherapy for HSV
Acyclovir (Zovirax) Valacyclovir (Valacyclovir),
pencyclovir Famcyclovir (Famvir),
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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.
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.
Human Herpes Viruses
1.HSV-1 and HSV-22.Varicella-zoster virus (VZV)3.Cytomegalovirus (CMV)4.HHV-6 and HHV-75.Epstein-Barr Virus (EBV)6.Kaposi’s sarcoma-associated herpesvirus
(KSHV,HHV-8)
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.
Herpes Labials or cold soar
Genital Herpes
• Lesions: vesicles, pustules, erythematous 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
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.
TREATMENT OF HERPES SIMPLEX ( COLD SORE ,GENITAL )
Human Herpes Viruses
1.HSV-1 and HSV-22.Varicella-zoster virus (VZV)3.Cytomegalovirus (CMV)4.HHV-6 and HHV-75.Epstein-Barr Virus (EBV)6.Kaposi’s sarcoma-associated herpesvirus
(KSHV,HHV-8)
VARICELLA ZOSTER VIRUS (VZV)
1. VARICELLA : CHICKEN POX
2. ZOSTER : SHINGLES
VZV causes two major syndromes
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
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
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
SHINGLES (Zoster)
•
Adapted from: gb.udn.com
HZ: Involvement of tip of nose is classic indicator of ocular involvement (Hutchinson’s sign)
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
ZOSTER IS VERY PAINFUL
There are three different ways to evaluating pain 1.Acute Pain :Pain at presentation that can be
quantified overthe first 30days2.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.
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
CMV disease• β Herpes virus dsDNA• Spread by repeated prolonged
exposure• CMV present in breast milk,
saliva, feces, urine, semen, cervical secretions
• Daycare centers• Once infected person carries
CMV for life.• Reactivation syndromes: T cell
mediated immunity compromised
Pneumonitis Bone marrow transplant
Colitis AIDS, solid organ
transplantation Retinitis
AIDS Hepatitis
SOT Nephritis
Kidney transplantation Mononucleosis: Congenital infection: IUGR,
microcephaly, chorioretinitis
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 15followed by 330 mg monthly as maintenance
Valacyclovir is approved for CMV in South Africa
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.
INDICATION
1) FDA Approved Indicationsa) Genital herpes simplex, Initial and recurrent episodesb) Herpes labialisc) Herpes zoster, Shinglesd) HIV infection - Recurrent genital herpes simplex, Suppressione) Recurrent genital herpes simplex, Suppression and transmission reductionf) Varicella
2) Non-FDA Approved Indicationsa) Genital herpes simplex, Initial and recurrent episodes - HIV infectionb) Herpes labialis - HIV infectionc) Herpes zoster, Shingles - HIV infection
•
Variation in indication USFDA vs MCC
DOSES In HSV & VZV
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.
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%
Side Effects
• Headache• Upset stomach, nausea• Diarrhea or loose stools• Constipation• Rash • Itching• Confusion• Yellowness of the skin or eyes• Fever• Blood in urine
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
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
SOME COMPARATIVE STUDY
Table 1. Recommended Regimens for Treatment of Herpes Simplex Virus in HIV-1-Infected Individuals
Dosage
Drug Episodic Therapy Suppressive Therapy
Acyclovir 400 mg orally 3 times per day for 5-10 days
400-800 mg orally 2-3 times per day
Famciclovir 500 mg orally 2 times per day for 5-10 days 500 mg orally 2 times per day
Valacyclovir 1,000 mg orally 2 times per day for 5-10 days 500 mg orally 2 times per day
Source: Centers for Disease Control and Prevention. Sexually Transmitted Diseases Treatment Guidelines, 2006. Morb Mortal Wkly Rep 2006;55:1-94.
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