|
|
|||
|
|||
|
|
|||
|
fda approval of havrix |
|||
|
|
|||
|
|||
 
|
|||
|
|
|||
|
fda approval of havrix Manufacturer: GlaxoSmithKline
HAVRIX is supplied as a sterile suspension for intramuscular administration fda approval of havrix. The vaccine is ready for use without reconstitution; it must be shaken beforeadministration since a fine white deposit with a clear colorless supernatantmay form on storage fda approval of havrix. After shaking, the vaccine is a slightly turbid white suspension fda approval of havrix. Each 1-mL adult dose of vaccine consists of not less than 1440 EL.U fda approval of havrix. of viralantigen, adsorbed on 0.5 mg of aluminum as aluminum hydroxide fda approval of havrix. There are 2 pediatric dose formulations, each with its own dosing schedule(see DOSAGE AND ADMINISTRATION ) fda approval of havrix. The formulations are: Not less than 360 EL.U fda approval of havrix. of viral antigen/0.5 mL; not less than 720 EL.U fda approval of havrix. of viral antigen/0.5 mL fda approval of havrix. Eachdose is adsorbed onto 0.25 mg of aluminum as aluminum hydroxide fda approval of havrix. The vaccine preparations also contain 0.5% (w/v) of 2-phenoxyethanol as a preservative fda approval of havrix. Other excipients are: Amino acid supplement (0.3% w/v) in a phosphate-bufferedsaline solution and polysorbate 20 (0.05 mg/mL) fda approval of havrix. Residual MRC 5 cellular proteins(not more than 5 mcg/mL) and traces of formalin (not more than 0.1 mg/mL) arepresent fda approval of havrix. Neomycin sulfate, an aminoglycoside antibiotic, is included in thecell growth media; only trace amounts (not more than 40 ng/mL) remain followingpurification fda approval of havrix.
Hepatitis A is highly contagious with the predominant mode of transmissionbeing person-to-person via the fecal-oral route fda approval of havrix. Infection has been shown tobe spread (1) by contaminated water or food; (2) by infected food handlers 2; (3) after breakdown in usual sanitary conditions or after floods or naturaldisasters; (4) by ingestion of raw or undercooked shellfish (oysters, clams,mussels) from contaminated waters 3 ; (5) during travel to areas of the worldwith poor hygienic conditions 4,5 ; (6) among institutionalized children andadults 6 ; (7) in day-care centers where children have not been toilet trained7 ; (8) by parenteral transmission, either blood transfusions or sharing needleswith infected people fda approval of havrix. 1 The level of economic development influences the prevalence of hepatitis Aand the age at which it is most likely to occur fda approval of havrix. In developing countries withpoor hygiene and sanitation, about 90% of children are infected by age 5 years fda approval of havrix. 1 As conditions improve, the prevalence decreases and the age at which infectionoccurs increases fda approval of havrix. Hence it is more likely to occur in adulthood, when diseaseis generally more severe and more likely to be fatal fda approval of havrix. 1 In the United States,attack rates for hepatitis A infection are cyclical and vary by population fda approval of havrix. The rates have increased gradually from 9.2 per 100,000 in 1983 to 14.6 per100,000 in 1989 fda approval of havrix. 8 The incubation period for hepatitis A averages 28 days (range: 15 to 50 days) fda approval of havrix. 9 The course of hepatitis A infection is extremely variable, ranging from asymptomaticinfection to icteric hepatitis fda approval of havrix. However, most adults (76% to 97%) become symptomatic fda approval of havrix. 10 Symptoms range from mild and transient to severe and prolonged and may includefever, nausea, vomiting, and diarrhea in the prodromal phase, followed by jaundicein up to 88% of adults, as well as hepatomegaly and biochemical evidence ofhepatocellular damage fda approval of havrix. 10 Recovery is generally complete and followed by protectionagainst HAV infection fda approval of havrix. However, illness may be prolonged, and relapse of clinicalillness and viral shedding have been described fda approval of havrix. 11 Hepatitis A infection is often asymptomatic in children under 2 years of age,who nonetheless excrete the virus in their stool and thereby serve as a sourceof infection fda approval of havrix. 10 In older patients and persons with underlying liver disease,it is generally much more severe fda approval of havrix. 1 This is reflected in mortality rates fda approval of havrix. Whilean overall case fatality rate of 0.6% has been reported, a case fatality rateof 2.7% has been reported in patients >/=49 years of age fda approval of havrix. 1 Indeed, while67% of cases occur in children, over 70% of deaths occur in those over the ageof 49 years fda approval of havrix. 1 There is no chronic carrier state fda approval of havrix. The virus replicates in the liver and isexcreted in bile fda approval of havrix. The highest concentrations of HAV are found in stools of infectedpersons during the 2-week period immediately before the onset of jaundice anddecline after jaundice appears fda approval of havrix. 12 Children and infants may shed HAV for longerperiods than adults, possibly lasting as long as several weeks after the onsetof clinical illness fda approval of havrix. 13 Chronic shedding of HAV in feces has not been demonstrated,but relapses of hepatitis A can occur in as many as 20% of patients, 1,14 andfecal shedding of HAV may recur at this time fda approval of havrix. 11 The presence of antibodies to HAV (anti-HAV) confers protection against hepatitisA infection fda approval of havrix. However, the lowest titer needed to confer protection has not beendetermined fda approval of havrix. In a chimpanzee challenge study, the quality of protection afforded by immuneglobulin (IG) prepared from initially seronegative human volunteers vaccinatedwith HAVRIX was comparable to that afforded by commercial IG fda approval of havrix. In this experiment,chimpanzees immunized with either preparation developed passive-active immunitywhen challenged with wild-type HAV fda approval of havrix. No animal in either group developed clinicalillness fda approval of havrix. In vitro studies in a randomly selected subset of human subjects (n = 80) showedanti-HAV induced by HAVRIX to have functional activity fda approval of havrix. This was demonstratedby a neutralization assay and a competitive inhibition assay using a panel ofmonoclonal antibodies known to have neutralizing activity fda approval of havrix. Immunogenicity in Adults: In 3 clinical studies involving over 400 healthyadult volunteers given a single 1440 EL.U fda approval of havrix. dose of HAVRIX, specific humoralantibodies against HAV were elicited in more than 96% of subjects when measured1 month after vaccination fda approval of havrix. By day 15, 80% to 98% of vaccinees had already seroconverted(anti-HAV >/=20 mIU/mL [the lower limit of antibody measurement by currentassay]) fda approval of havrix. Geometric mean titers (GMTs) of seroconverters ranged from 264 to 339mIU/mL at day 15 and increased to a range of 335 to 637 mIU/mL by 1 month followingvaccination fda approval of havrix. 15 The GMTs obtained following a single dose of HAVRIX are at least several timeshigher than that expected following receipt of IG fda approval of havrix. In a clinical study using 2.5 to 5 times the standard dose of IG (standarddose = 0.02 to 0.06 mL/kg), the GMT in recipients was 146 mIU/mL at 5 days post-administration,77 mIU/mL at month 1, and 63 mIU/mL at month 2 fda approval of havrix. 15 In 2 clinical trials in which a booster dose of 1440 EL.U fda approval of havrix. was given 6 monthsfollowing the initial dose, 100% of vaccinees (n = 269) were seropositive 1month after the booster dose, with GMTs ranging from 3,318 mIU/mL to 5,925 mIU/mL fda approval of havrix. The titers obtained from this additional dose approximate those observed severalyears after natural infection fda approval of havrix. In a subset of vaccinees (n = 89), a single dose of HAVRIX 1440 EL.U fda approval of havrix. elicitedspecific anti-HAV neutralizing antibodies in more than 94% of vaccinees whenmeasured 1 month after vaccination fda approval of havrix. These neutralizing antibodies persisteduntil month 6 fda approval of havrix. One hundred percent of vaccinees had neutralizing antibodieswhen measured 1 month after a booster dose given at month 6 fda approval of havrix. Immunogenicity of HAVRIX was studied in subjects with chronic liver diseaseof various etiologies fda approval of havrix. 189 healthy adults and 220 adults with either chronichepatitis B (n = 46), chronic hepatitis C (n = 104), or moderate chronic liverdisease of other etiology (n = 70) were vaccinated with HAVRIX 1440 EL.U fda approval of havrix. ona 0- and 6-month schedule fda approval of havrix. The last group consisted of alcoholic cirrhosis (n= 17), autoimmune hepatitis (n = 10), chronic hepatitis/cryptogenic cirrhosis(n = 9), hemochromatosis (n = 2), primary biliary cirrhosis (n = 15), primarysclerosing cholangitis (n = 4), and unspecified (n = 13) fda approval of havrix. At each time point,GMTs were lower for subjects with chronic liver disease than for healthy subjects fda approval of havrix. At month 7, the GMTs ranged from 478 mIU/mL (chronic hepatitis C) to 1,245 mIU/mL(healthy), as determined by a commercial ELISA fda approval of havrix. The relevance of these datato the duration of protection afforded by HAVRIX is unknown fda approval of havrix. One month afterthe first dose, seroconversion rates in adults with chronic liver disease werelower than in healthy adults fda approval of havrix. However, 1 month after the booster dose at month6, seroconversion rates were similiar in all groups; rates ranged from 94.7%to 98.1% fda approval of havrix. Immunogenicity in Children and Adolescents: In 6 clinical studies involvingpediatric vaccinees (n = 762) ranging from 1 to 18 years of age, the GMT following2 doses of HAVRIX 360 EL.U fda approval of havrix. given 1 month apart ranged from 197 to 660 mIU/mL fda approval of havrix. Ninety-nine percent of subjects seroconverted following 2 doses fda approval of havrix. When a booster(third) dose of HAVRIX 360 EL.U fda approval of havrix. was administered 6 months following the initialdose, all subjects were seropositive 1 month following the booster dose, withGMTs rising to a range of 3,388 to 4,643 mIU/mL fda approval of havrix. In 1 study in which childrenwere followed for an additional 6 months, all subjects remained seropositive fda approval of havrix. Solicited adverse effects were similar in frequency and nature to those seenfollowing administration of ENGERIX-B ® [Hepatitis B Vaccine (Recombinant)] fda approval of havrix. In 4 clinical studies, children and adolescents (n = 314), ranging from 2 to19 years of age, were immunized with 2 doses of HAVRIX 720 EL.U./0.5 mL given6 months apart fda approval of havrix. One month after the first dose, seroconversion ranged from 96.8%to 100%, with GMTs of 194 mIU/mL to 305 mIU/mL fda approval of havrix. In studies in which sera wereobtained 2 weeks following the initial dose, seroconversion ranged from 91.6%to 96.1% fda approval of havrix. One month following a booster dose at month 6, all subjects were seropositive,with GMTs ranging from 2,495 mIU/mL to 3,644 mIU/mL fda approval of havrix. 15 In 1 additional study in which the booster dose was delayed until 1 year followingthe initial dose, 95.2% of the subjects were seropositive just prior to administrationof the booster dose fda approval of havrix. One month later, all subjects were seropositive, with aGMT of 2,657 mIU/mL fda approval of havrix. 15 Also, HAVRIX has been found to be highly efficacious in a clinical study ofchildren at high risk of HAV infection (see below) fda approval of havrix. At present, the duration of protection afforded by HAVRIX has not been established fda approval of havrix. Therefore it is unknown if the protection provided to immunized children willlast until adulthood fda approval of havrix. |
|||
 
|
|||
|
|
|||
|
|
|||
|
|
|||
|
|
|||
|
|
|||
| ffda approval of havrix fdda approval of havrix fdaa approval of havrix fda approval of havrix fda aapproval of havrix fda appproval of havrix fda appproval of havrix fda apprroval of havrix fda approoval of havrix fda approvval of havrix fda approvaal of havrix fda approvall of havrix fda approval of havrix fda approval of havrix fda approval oof havrix fda approval off havrix fda approval of havrix fda approval of hhavrix fda approval of haavrix fda approval of havvrix fda approval of havrrix fda approval of havriix fda approval of havrixx da approval of havrix fa approval of havrix fd approval of havrix fdaapproval of havrix fda pproval of havrix fda aproval of havrix fda aproval of havrix fda appoval of havrix fda apprval of havrix fda approal of havrix fda approvl of havrix fda approva of havrix fda approval of havrix fda approval of havrix fda approval f havrix fda approval o havrix fda approval ofhavrix fda approval of avrix fda approval of hvrix fda approval of harix fda approval of havix fda approval of havrx fda approval of havri f da approval of havrix fd a approval of havrix fda approval of havrix fda approval of havrix fda a pproval of havrix fda ap proval of havrix fda app roval of havrix fda appr oval of havrix fda appro val of havrix fda approv al of havrix fda approva l of havrix fda approval of havrix fda approval of havrix fda approval of havrix fda approval o f havrix fda approval of havrix fda approval of havrix fda approval of h avrix fda approval of ha vrix fda approval of hav rix fda approval of havr ix fda approval of havri x fda approval of havrix dfa approval of havrix fad approval of havrix fd aapproval of havrix fdaa pproval of havrix fda paproval of havrix fda approval of havrix fda aprpoval of havrix fda apporval of havrix fda apprvoal of havrix fda approavl of havrix fda approvla of havrix fda approva l of havrix fda approval of havrix fda approval o f havrix fda approval fo havrix fda approval o fhavrix fda approval ofh avrix fda approval of ahvrix fda approval of hvarix fda approval of harvix fda approval of havirx fda approval of havrxi afda approval of havrix thefda approval of havrix fda approval of havrix | |||
|
|
|||
|
|
|||
|
|
|||
|
Copyright 2005 D-S LTD. |
