US Infectious Disease 2007 - Issue II

Virazole_ad2.qxp 5/11/07 11:55 Page 38
IN THE RABBIT AT DAILY ORAL DOSE LEVELS AS LOW AS MGKG6)2!:/,%.O TERATOGENICTREATMENT IN SIX OF SIX ADULTS WITH CHRONIC30OBSTRUCTIVE!'
AEROSOLLUNGGENERATOR !DMINISTRATION BY FACE MASK OR OXYGEN TENT
EFFECTS WERE EVIDENT IN THE RABBIT AND RAT ADMINISTEREDDISEASEDAILY ORALANDDOSESIN FOUROOFF SIX ASTHMATIC ADULTS $YSPNEA ANDMAYCBHESTE NECESSARYSORENESSIF A HOOD CANNOT BE EMPLOYED SEE 30!'
MANUAL
ANDMGKG RESPECTIVELY WITH ESTIMATED HUMANWEREEQUIVALENTALSO REPORTEDDOSESIN THE LATTER GROUP -INOR ABNORMALITIES(OWEVERINPULMONARTHE VOLUMEY AND CONDENSATION AREA ARE LARGER IN A TENT AND THIS
OF AND MGKG BASED ON BODY SURFACE AREAFUNCTIONADJUSTMENTWERESEEALSO SEEN IN HEALTHY ADULT VOLUNTEERS MAY ALTER DELIVERY DYNAMICS OF THE DRUG
0HARMACOKINETICS 4HESE DOSES ARE CONSIDERED TO DEFINE
)N THE
T
ORIGINAL
HE h.O
STUDY POPULATION OF APPROXIMATELY-ECHANICALLY INFANTS6ENTILATEDWHO)NFANTS
/BSERVABLE 4ERATOGENIC %FFECTS ,EVELv ./4%, T FOR RIBAVIRIN
RECEIVED
IN
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6)2!:/,% SEVERAL SERIOUS
4HE
ADVERSE
RECOMMENDED
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DOSE AND ADMINISTRATION SCHEDULE FOR INFANTS WHO
AND RAT
OCCURRED IN SEVERELY ILL INFANTS WITH LIFE
THREATENINGSES REQUIREUNDERLYINGMECHANICALDISEA VENTILATION IS THE SAME AS FOR THOSE WHO DO NOT
&OLLOWING ORAL ADMINISTRATION OF RIBAVIRIN IN THEMANYPREGNANTOF WHOMRAT REQUIRED ASSISTED VENTILATION 4HE ROLE%ITHEROF 6)2!:/,%A PRESSUREINOR VOLUME CYCLE VENTILATOR MAY BE USED IN CONJUNCTION
MGKG AND RABBIT MGKG MEAN PLASMALEVELSM THESEOF DRUGEVENTSRANGEDISFROINDETERMINATE 3INCE THE DRUGS AWITHPPROVALTHE 3IN0!'
)N EITHER CASE PATIENTS SHOULD HAVE THEIR ENDOTRACHEAL

—-;
—M,= AT HOUR AFTER DOSING TO UNDETECTABLEADDITIONAL REPORTS OF SIMILAR SERIOUS THOUGH NON
FATALN TUBESEVENTSSUCTIONEDHAVE BEEEVERY
HOURS AND THEIR PULMONARY PRESSURES
LEVELS AT HOURS !T HOUR FOLLOWING THE ADMINISTRATIONFILED IOFNFREQUENTLY OR %VENTS ASSOCIATED WITH AEROSOLIZEDMONITORED6)2!:/,%FREQUENTLYUSE EVERY
HOURS &OR BOTH PRESSURE AND VOLUME
MGKG IN THE RAT AND RABBIT ./4%, RESPECTIVELY MEANHAVEPLASMAINCLUDEDLEVELSTHE FOLLOWING VENTILATORS HEATED WIRE CONNECTIVE TUBING ANDSIBNACTERIA FILTERS IN SERIE
OF DRUG IN BOTH SPECIES WERE NEAR OR BELOW THE LIMIT OF DETECTION
0ULMONARY

7ORENINGS OF RESPIRATORY STATUS
THE EXPIRATORY LIMB OF THE SYSTEM WHICH MUST BE CHANGED FREQUENTLY IE
—- SEE 0HARMACOKINETICS
BRONCHOSPASM PULMONARY EDEMA HYPOVENTILATION
EVERY HOURS MUST BE USED TO MINIMIZE THE RISK OF 6)2!:/,%
!LTHOUGH CLINICAL STUDIES HAVE NOT BEEN PERFORMED 6)2!:/,%CYANOSISMAYDYSPNEA BACTERIAL PNEUMONIA PNEUMOTHORAX
PRECIPITATION IN THE SYSTEM AND THE SUBSEQUENT RISK OF VENTILATOR
CAUSE FETAL HARM IN HUMANS !S NOTED PREVIOUSLYD RIBAVIRIN ISAPNEACONCENTRATEATELECTASIS AND VENTILATOR DEPENDENCE
DYSFUNCTION 7ATER COLUMN PRESSURE RELEASE VALVES SHOULD BE USED IN
IN RED BLOOD CELLS AND PERSISTS FOR THE LIFE OF THE CELL 4HUS
#ARDIOVASCULAR
THE TERMINAL
#ARDIAC ARREST HYPOTENSION BRADYCARDIA
THE VENTILATOR CIRCUIT FOR PRESSURE CYCLED VENTILATORSED AND MAY BE UTILIZ
HALF
LIFE FOR THE SYSTEMIC ELIMINATION OF RIBAVIRINFTHEIS ESSENTIALLY
AND DIGITALIS
THAT O
TOXICITY "IGEMINY BRADYCARDIA AND
WITH
TACHYCARDIA
VOLUME CYCLED VENTILATORS 3%% 30!'
-!.5!, &/2 $%4!),%$
HALF
LIFE OF CIRCULATING ERYTHROCYTES 4HE MINIMUM INTERVAL
HAVE BEEN
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).3425#4)/.3
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6)2!:/,%
S
BRAND
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FOR (EALTH #ARE 0ERSONNEL
DIFFICULTIES DUE TO INADEQUATE VENTILATION AND
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GAS EXCHANGE
PER M, VIAL FOR AEROSOL ADMINISTRATION ONLY "Y
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0RECIPITATION OF DRUG WITHIN THE VENTILATORY APPARATUSDO
STERILE
INCLUDING
TECHNIQUE
THE EN
RECONSTITUTE DRUG WITHOFASTERILEMINIMUM OF M,
6)2!:/,% HAS BEEN SHOWN TO BE TOXIC TO LACTATING ANIMALSTRACHEALANDTUBETHEIRHAS RESULTED IN INCREASED POSITIVEE END
530
EXPIRATORY
WATER FOR INJECTION
PRESSUR
OR INHALATION IN THE ORIGINAL M, GLASS VIAL
OFFSPRING )T IS NOT KNOWN IF 6)2!:/,% IS EXCRETED INANDHUMANINCREASEDMILK POSITIVE INSPIRATORY PRESSURE !CCUMULATION
3HAKE WELL4R
OF
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F
N
LUID
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IN
THE CLEAN STERILIZED M, 30!'
RESERVOIR
AND FURTHER DILUTE TO A FINAL VOLUME OF M, WITH 3TERILE 7ATER FOR
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TUBING hRAIN OUTv HAS ALSO BEEN NOTED -EASURES TO AVOID THESE
)NJECTION 530 OR )NHALATION 4HE FINAL CONCENTRATION SHOULD BE
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COMPLICATIONS
RECEIVING
SHOULD BE FOLLOWED CAREFULLY SEE $/3!'% !.$
MGM,)MPORTANT 4HIS WATER SHOULD ./4 HAVE HAD ANY ANTIMICROBIAL
AEROSOLIZED 6)2!:/,% SHOULD BE AWARE THAT RIBAVIRIN
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HAS BEEN SHOWN
4)/.
AGENT OR OTHER SUBSTANCE ADDED 4HE SOLUTION SHOULD BE INSPECTED
TO BE TERATOGENIC IN ALL ANIMAL SPECIES IN WHICH ADEQUATE
(EMATOLOGIC
STUDIES HAVE
VISUALLY FOR PARTICULATE MATTER AND DISCOLORATIONON PRIOR TO ADMINISTRATI
BEEN CONDUCTED RODENTS AND RABBITS !LTHOUGH!LTHOUGHNO REPORTSANEMIAOF WAS NOT REPORTED WITH USE OF
3OLUTIONS
AEROSOLIZED
THAT HAVE BEEN PLACED IN THE 30!'
UNIT SHOULD BE
TERATOGENESIS IN OFFSPRING OF MOTHERS WHO WERE EXPOSED6)2!:/,%TO AEROSOLIZEDIN CONTROLLED CLINICAL TRIALS MOST INFANTS
DISCARDED
TREATED W
AT
ITH
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THE
EVERY HOURS AND WHEN THE LIQUID LEVEL IS LOW BEFORE
6)2!:/,% DURING PREGNANCY HAVE BEEN CONFIRMEDAEROSOLNO CONTROLLEDHAVE NOT BEEN EVALUATED TO WEEKS POST
TREATMENT
ADDING NEWLY
WHEN
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STUDIES HAVE BEEN CONDUCTED IN PREGNANT WOMEN 3TUDIESANEMIAOFISENVIRON
LIKELY TO OCCUR !NEMIA HAS BEEN SHOWN TO
(/7
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FREQUENTLY
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DISPERSE INTO THE IMMEDIATE BEDSIDE AREA DURING ROUTINECASESPATIENTOF ANEMIACARETYPE UNSPECIFIED RETICULOCYTOSIS
6)2!:/,%
AND HEMOLYTIC
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PACKS CONTAINING M, GLASS VIALS WITH GRAMS OF 3TERILE LYOPHILIZED
ACTIVITIES WITH HIGHEST AMBIENT LEVELS CLOSEST TO
THE PATIENTANEMIAAASSOCIATEDND EXTREMEWITH AEROSOLIZED 6)2!:/,% USE HAVE
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.$#
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ITH
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/THER
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30!'
6IALS CONTAINING THE LYOPHILIZED DRUG POWDER SHOULD BE STORED
HAVE DOCUMENTED AMBIENT DRUG CONCENTRATIONS AT THE
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AND
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# &
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6)2!:/,%
FOR
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#
& FOR HOURS 3OLUTIONS WHICH
SITIVE ANIMAL SPECIES

EXPERIMENTAL INTRAVENOUS 6)2!:/,% THERAPY HAVE ALSOHAVEBEENBEENREPORTEDPLACED IN THE 30!'
UNIT SHOULD BE DISCARDED AT LEAST EVERY
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3AFETY AND (EALTH .)/3( DEMONSTRATED MEASURABLE URINE LEVELS OF
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O
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CARE
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OR
HAVE REPORTED EXPERIENCING ADVERSE#HEMOTHEREVENTS THROUGH

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POST
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A
)/3(
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NINE IN EXPOSED WORKERS (OWEVER THE RELATIONSHIP

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URINARY
3EVERAL CASES OF BRONCHOSPASM ANDOR
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CHEST P
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AIN WERE

RIBAVIRIN LEVELS IN EXPOSED WORKERS PLASMA LEVELS IN
ALSO
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AND
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THE SPECIFIC RISK OF TERATOGENESIS IN EXPOSED PREGNANT
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IS
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TREATMENT
LENSES
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-ED
HAVE

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)T IS GOOD PRACTICE TO AVOID UNNECESSARY OCCUPATIONAL
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TO
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TO
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6)2!:/,% (EALTH CARE WORKERS WHO ARE PREGNANT SHOULD CONSIDER
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4HE SYMPTOMS
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OF 236 IN ADULTS CAN INCLUDE

HEADACHE
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CLOSE PATIENT CONTACT CANNOT BE AVOIDED PRECAUTIONS
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CONGESTION
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AND WHEEZING ALTHOUGH 236 INFECTIONS
2IBAVIRIN
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IN
ARE
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MILD AND TRANSIENT 3UCH INFECTIONS REPRESENTRD
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HAZA

PER HOUR THE USE OF 6)2!:/,% AEROSOL SCAVENGINGF DEVICES
TO UNINFECTED
TURNING
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OF
PATIENTS )T IS UNKNOWN WHETHER CERTAIN SYMPTOMS
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DEVICE FOR TO MINUTES PRIOR TO PROLONGED
CITED IN R
PATIENT
EPORTS FROM HEALTH CARE WORKERS WERE DUE TO

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TO
OHN
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CONTACT AND WEARING APPROPRIATELY FITTED RESPIRATOR
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OR INFECTION
3URGICAL
WITH 236 (OSPITALS SHOULD IMPLEMENT
&LORIDA
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(EALTH AND (UMAN 3ERVICES 0UBLIC (EALTH 3ERVICE #ENTERS FOR .)/3(
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AND 4ECHNICAL
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!SSISTANCE "RANCH AND ADDITIONAL RECOMMENDATIONS HAVE.O OVERDOSAGEBEEN PUBLISHEDWITH 6)2!:/,% BY AEROSOL ADMINISTRATION
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"% !$-).)34%2%$
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4).'
WHO
$%6)#%
6ALEANT0HARMACEUTICALS.ORTH!MERICA
EXPERIENCED WORSENING RESPIRATORY STATUS RELATED TO BRONCHOSPASM
4HE RECOMMENDED
WHILE
TREATMENT REGIMEN IS MGM,6)2!:/,% AS THE
(YLAND!VE
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STARTING
BEEN ATTRIBUTED
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TO
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MECHANICAL VENTILATOR MALFUNCTION IN WHICH 6)2!:/,%IN
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FOR A HOUR DELIVERY PERIOD WOULD BE
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OF
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