Document 2421

P r n -a UPDATE
Editors: Mr. Nasser Al Shehri, B.Sc. Pharm;
Dr. Ashraf A1 Mwan, Ph,D.
Guidelines for Dosing Aminoglycoside
in Adult
By: AliAl-Mitwazi, Pharm D,
infectious is^ Clinical Hwnnacist.
I ".1 d
s are corn
prescribed in clinical practice for
of different and wide range of
diseases. These diseases range fkom mild
life threatening infection. Since
undmgo a specialway of dose c
monitoring, it is an obvious that aploper an& .*
beet way is demanded to carty out the
course of treatment with these drugs. This
will become of most help in orderto optimizeb
their use, decrease the possible development .
andminimize as much
. ' as possible the development of different
kinds of toxicities (e.g.: Ototoxicity,. '
Nephrotoxicity, Electrolytes
disturbances.. ..etc.) associated with wrong
dosing and/or monitoring. Anti-microbial
subcommittees have made these dosine
guideline in order to standardized
facilitate dosing and monitoring of these
antibiotics in l&-I. Both guidelines were
discussed and approved in antimicrobial
subcommittee in June, 2004 and approved by
P&T committee in September, 2004. For
further clarification,
Pharmacy Upc*r!e,
Volume 12, No. 4
Aminoglywskies GtlideUnes
CQ&Z lphibltar W n d p Porn
Clinical Worn: Idant ~okulisrn
FAQ: ~ e n l n ~ o e o &Vac~lne
ik ~ e p r t m e n t
ou can contact the InfectiousDiseases team
r clinical services at the pharmacy
epartmentfor pn~r-ssistance.
$%tie& n&sBigtbb
4 Eridocartlitis
,4 ~ ~ ~ ~
Y 4 CNS ipfedion
Surgical prophylaxis
Cystic fibrosis.
Cr-CI < 40 mU min
1. Calculate Ideal Body Weight (IBW)
IBW (males) = 50 kg + 2.3 kg (for every
2.54 cm above 152.4 cm).
JBW (females) = 45.5 kg + 2.3 kg (for every
2.54 cm above 152.4 cm).
If Total Body Weight (TBW) less than
IBW then use TBW.
For obese patients use the Adjusted Body
Weight (ABW):
ABW=IBW+ 0.4 (TBW- IBW).
2. Estimate Creatinine Clearance
(CrCl) mllmin*
CrCl (males) =
renal function, you need to obtain level
every 5 days.
b If the level is abnormal, contact the
clinical pharmacist, infectious diseases
team or clinical microbiologist for dose
Failure to adhere to monitoring
guideline, the lab will cancel the
* Target range:
(140 age) x IBW x 1.22
Strum Crcatininc
CrCl (females) =
(140 -age) x IBW x 1.22
X 0.85
Senun Creatinine
* Unit of Serum Creatinine in
N.B.: Physicians/ clinical pharmacists
are encouraged to use ODD unless the
patient is not eligible.
3. Determine the dose
Use IBW for the dosing of
2rCI (mllmin)
> 80
1. Calculate Ideal Body Weight (IBW)
Dose (melkd I24 h
As above
If TBW less than IBW then use
For obese patients use the adjusted body
weight (ABW):
4. Serum concentration monitoring:
b Request justifications( i.e. is the patient
ondialysis, renal failure, ODD,C.D etc)
Sampling within lab working hours 7:30
A M - 4:30 P.M.Saturday - Wednesday.
Duration of treatment greater than 3
Obtain pme-leveljust before the 2nd dose
and no need for ueak level.
~ v o i d ~ ~ m ~ l i nthe
~ f same
r o mantibiotic
infusion lineunlessit is not feasible. then
flush the line with sterile saline.
If normal, repeat the level every 7 days
and obtain senun creatinine and BUN
twice weekly.
Repeat the level if there is a change in
serum creatinine or change in the dose or
tkquency or concomitant nephrotoxic
agents, or
Use I B W unless the patient is
2. Estimate Creatinine clearance:
As above.
3. Determine the dose & the interval
b Use IBW for dosing Amiioglycosides
Sever life-threatening infection 2 mgl kg
i.5 mg/kg (IBW).
b Synergy (gram- positive infection) 1 mgl
kg (IBW).
Phannacy Update, Volume 12, No. 4
agents, or medical condition affecting
renal function.. vou
. need to obtain level
every5 days.
Failure to adhere to monitoring
guideline, the lab will cancel the
Target level is:
I Tt.ough
Doses: Gentamicin 3 mg 1 kg (IBW)
every 8 hrs & Netilmicin 3.5 mg 1 kg
(IBW) every 8hrs for patients with
b. Amikacin:
Usual dose 5 - 7.5 mgl kg (IBW)
overv 12 hours
20 - 39 mumit
Every 24 hours
follow the level
10 mg 1kg (IBW) every 8hrs for
patients with cysticfibrosis.
4. Serum concentration monitoring:
Request justifications (i.e. is the patient
on dialysis, renal failure, ODD, C.D.
Sampling within lab working hours 7:30
A.M. - 4:30P.M. Saturday - Wednesday.
Duration of treatment greeter than 3
Avoid sampling from the same antibiotic
infusion line, unless not feasible, then
flush the line with sterile saline.
Obtain drug level at the 4th dose (time to
reach steady state) unless renal
dysfunction suspected.
Obtain pre-dose level (trough) just
before the 4th dose.
Obtain post-dose level (peak) 30 minutes
after end of infusion of4th dose.
If level is normal, repeat the level every 7
days, and obtain serum Creatinine &
BUNtwice weekly.
If the level is abnormal, contact the
clinical pharmacist, infectious disease or
clinical microbiology for dose
Repeat the level if there is a change in
serum Creatinine or change in the dose or
frequency or concomitant nephrotoxi
Pharmacy U$afe, Volume 12, No. 4
5. Dosing for patient nm
1. Gentamicin & Netilmicin:
* Check the level after dialysis to guide
you for dosing.
Give 1mg/ kgpost dialysis
2. Amikacin:
* Check the level after dialysis to guide
you for dosing.
Give 5 mglkgpost dialysis
B. Peritoneal dialysis
1. Gentamicin & Netilmicin:
Dose as of CrCl of < 20 mV min and
follow level
Give 4 mg per liter lost of dialysate per
day 1.V. as supplement dose for CAPD
(e.g. 8 literlday lost, give 32 mg/ day)
2. Amikacin
Dose as ofCrCl <20mVmin
give 20 mgper liter lost of dialysate per
day LV. as supplement dose for CAPD
(e.g. 8 literlday lost, give 160mglday)
:ontinous Arteriovenous or
Venovenous Hernofiltration
1. Gentamicin & N e W c i n :
Dose as for Crcl25 mVmin
2. Amikacin
Dose as for Crcl25 mVmin
** Calculating an appropriate maintenance
dose for Aminoglycoside during dialysis is
diff~cuulThe best guide is to obtain level to
minimize toxicity.
Mr. Nasser Al-Shehri, DZC
In the previous issue ofthe Pharmacy Update (Vol12,(3): 3), we published about the new safety data of
Rofecoxib (VioxxB, MSD), a member of a class called COX2 inhibitors, which has been withdrawn
voluntarily from the market by Merck in September2004 based on a new facts that patients taking high dose
~ofecoxib(more than25 mg per day) had triple the risk of heart attacks, Acute ~ ~ o c a r d iinfarction
or Sudden Cardiac Death (SCD). In addition to that, it's been concluded fiom that survey that patients taking
lower doses of Rofecoxib were possibly more likely to suffer these seriousheart problems than other
including those taking any other dose of Celecoxib, another member in the same class. However, the risk
didn't appear to be significant.Another COX2 inhibitor, Valdecoxib @extraTM,Pfizer) has been reported to
have life threatening skin reactions like Toxic epidermal necrolysis (TEN) and Stevens-Johnson Syndrome
(SJS) (by November 2004, FDA received reports of 87 cases). BextraTMhas also been reported to increase
cerebrovascular risks in a study which included over 1500patients treated for acute pain in the setting ofpost
CoronaryArtery Bypass Grafting (CABG) compared to placebo.
Nowadays, a new safety information about Celecoxib (CelebrexB, Pfizer), showed that the drug may
cany the same risk of fatal and non-fatal cerebrovascular events (composite end point of cardiovascular
(CV) death, AM1and stroke).
In one large, long term cancer prevention trial (24uu patients), Data Safety Monitoring Board, based on
an interim analysis, showed that patients who were randomized to receive Celecoxib have an increased CV
riskwhencompared to placebo. CVcasesreportedat the interim analysis were as follow:
BI Placebo group: 6 CV cases.
Celecoxib 200mg bid: 15 CV events (2.5 folds increase over placebo).
6l Celecoxib 400mg bid: 20 CV events (3.4 folds increase over placebo).
Theses information were received by Pfizer on the night of the 16th of December 2004 and have
been shared by the company with Health Canada, the U.S. FDA as well as European Medicines Agencies
EMEA. The trial was called the Adenoma Prevention with Celelcoxib (APC). Objective ofthis study was to
investigate whether Celecoxib could prevent colon cancer in people who had previously had colon polyps.
The studv was exoected to comolete in the Sorine of 2005. however. based on the results of the interim
analysis,$e ~ a t i o i acancer
~ n s h t (NcI)
stippidthis triai.
A seoarate trial soonsored by Pfizer called Prevention of Svontaneous Adenoma Polms (PreSAP)
doesn't appear to con& this risk. This trial has also been stoppeddased on the safety data of C~APC
trial. A
third trial, however, the Alzheimer's Disease Anti-Inflammatory Prevention Trial (ADAPT), is still
continuing regardless of the results of the APC trial. These two latter trials are similar in size and duration to
theAPC trial.
FDA has advised physicians to consider riskhenefit assessment for individual patients' therapy, and to
use the lowest effective dose once decided to give Celecoxib. Health Canada has withdrawn the market
Authorization for the use of Celecoxib in Familial Adenomatous Polyposis (FAP). Pfizer requested
physicians to contact patients already using Celecoxib in FAP and advised them to immediately discontinue
the medication and to continue observing these patients according to standard medical practice. A thorough
evaluationof the entire class has been promised by differenthealth regulatory agenciesto release more safety
data especially about the cardiovascularrisks.
Pharmacy Updafe, Yolume 12, No. 4
By: Ms. MonaAl-Humyyen. Phunn. MS',
A/ Supewr For of the Drug Infomution Center
Infantile botulism is an infectious
neuropari?lytic illness of infants caused by intestinal
absorption of toxin type A and B produced by
ingestion of the spore-forming, anaerobic, grampositive bacilli Clostridium botulinum, which is
found globally in soil or honey products and
characterized by constipation, poor feeding, and
failure to thrive that may be followed by progressive
weakness, impaired respiration, and death. Physician
awareness of infant botulism is paramount to early
recognition and intervention, because more than 70
percent of these infants will eventually require
mechanical ventilation.
Infant botulism results from ingestion of
botulinal spores. In -85% of cases the source is
unknown. The botulinum toxin binds with the
presynaptic area of the neuromuscular junction, as
well as at other cholinergic synapses, and prevents
acetylcholine release. The disease has an identifiable
progression. Any stress or added insult can result in
total neuromuscular blockade and precipitate
respiratory arrest and death by causing hypotonia and
descending symmetric flaccidparalysis.
Infantile botulism occurs in infants aged 4 2
months with a peak incidence between 2 and 6
months. 90% of the worldpcases of infant botulism
are younger than six months and diagnosed in the
United States. As of 1996, the Center for Disease
Control and Prevention (CDC) has documented more
than 1,400 cases. Soil and honey contamination are
the two recognized sources of botulinum spores (A
history of honey consumption is seen in 15% of the
botulism cases reportedto CDC).
Infant botulism may be difficult to recognize
because of its insidious onset. The classic clinical
features include constipation, cranial nerve
abnormalities, weakness, weak q,
p&r feeding,
.. .
An infant with botulism is often diagnosed
with sepsis or meningo-encephalities.Dehydration
Pharmacy U$ate, Volume 12, No. 4
and other metabolic causes should be properly
investigated. Reye's syndrome can be effectively
ruled out by determining the serum ammonia level.
Poisoning also must be considered. Lastly, acute
upper airway obstruction should be considered in
infant with poor feeding, an inability to handle
secretionsand respiratorydistress.
A definitive diagnosis can be made with the
detection of botulism toxin and the isolation of
C.botulinum£tomstool samules.
In addition, electromyogr& (EMG) studies can
support an early diagnosis.
Clinical Management:
1. Therapy consists of meticulous and aggressive
supportive care, particularly ventilatory support,
pulmonaryhygiene, andnutrition.
2. The child should be admitted to an intensive care
unit and monitored for apnea, bradycardia,
ventilatory insuficiency, and complications.
3. Most patients require IV fluids to maintain
A human derived antitoxin has successfully reduced
the time spent in the hospital & the need for
mechanical ventilation & tube feeding.
Dose: lmL/kg (50 mgntg) as single IV infusion
over 1to 2 has soon as clinicaldiagnosis is made.
Aminoglycosides and other agents that may
precipitate or exacerbate neuromuscular blockage
should be used with extreme caution in hypotonic
infants until the cause of the hypotonia is clearly
identified: these agents are contraindicated in infant
I m ~ o r t a nNotes
The prognosis is excellent, with a case- fatality rate
Forinfants whorequiremechanicalventilation,the
average duration is 23 days. And 51 days from
admission were able to feedorally.
The average hospital stay is44 days.
Most relauses occurred within 13 davs of hosnital
discharge. 'herefore, close follow-upis impc&nt
during the first month after discharge.
By: Mr. Nasser AlNhehri, B.Pharm Drug
Information Center Pharmacist
For more information contact:
Q: What is meningococcalvaccine, why is it needed?
A: A lyophiliied preparation of purified polysaccharide from Neisseria meningitides (meningococci) of different
serogroups. Meningococcal vaccines are used for active imrnunisation against Neisseria meningitidis infections which
include meningitis and septicaemia in high risk groups. Those high risk groups include people living or traveling to
areas where the disease is endemic or highly endemic. It is also recommended for people who live in close contacts of
patients with the disease. Persons who have terminal complement component deficiencies and those who have
functional or anatomic asplenia are also included in this high risk groups. Personnel (industrial, research, lab.. .etc) who
are exposed to N.meningitidis in solutions that may be aerosoliied also should be considered for vaccination.
N.meningitides can spreadby respiratory droplets, not aerosols; hence close contact can increase the chance of catching
the disease. The vaccine is a requirement of the ministry of health for people who wish to visit Saudi Arabia for the
purpose of pilgrimage (Hajj) or Umrah, since this infection can be picked up by fellow travelers in such crowded
atmosphere.All arrivals must present acertificate of vaccination against meningitis issuednot more than 3 years andnot
less than lodays.
Q: How many kinds of the vaccine are available?
A: Different kinds of meningococcal vaccines depend on the types of N. meningitides serogroups they are prepared from.
Previously in RKH, we used to have the Bivalent vaccine, which cover for serogroups A and C N.meningitedes.
SerogroupAN.meningitides is the one responsible for the frequent outbreaks of meningitis infection in the meningitis
belt ofAfrica which encompassesEthiopia in the east to Senegal in the west. Frequent outbreaksthat tookplace between
1990 and 1993 in North America was because of Serogroup C. Nowadays, we have the tetravalent meningococcal
Vaccine (MencevaxtOACWY, GlaxoSmithKline) which can give protection against SerogroupsA, C, W135 andY. The
importance of such vaccine became obvious since the outbreak occurred in Hajj 2000 which generated particular
international interest in SeogroupW 135that caused the disease.
Q: How does this Vaccine administered?
A: The vaccine is administered by SC injection in a dose of 0.5 ml (representing 50 mcg of each of the polysaccharides of
groups A, C, Y & W135) single dose for adults and children over the age of 2 years. Protective antibody levels are
achieved in 7 to 15 days and may persist for up to 5 years. Revaccination may he necessary after aperiod of 3 to 5 years
to ensure optimal protection.
Q: Can this Vaccine (ACW135,Y) given to pregnant and lactating women?
A: Pregnancy or breast feeding is not a contraindication to vaccination. However, the vaccine should not he given to
pregnant women unless they are at definite risk from groups ofA, C, Y & W135 to cope with the general principles.
Adequate human data on use during lactation and adequate animal reproduction studies are not available.
Q: What is the age group recommendations for giving thevaccine?
A: The vaccine is recommended for use in adults and children above 2 years of age. The seroconversions of the vaccine in
these age groups meet with the latest recommendations of the WHO for the four serogroups of the vaccine (90%
seroconversion which consider the fourfold increase in bactericidal antibody titer as the minimum threshold for
seroconversion). Children as young as 6 months showed weak response to the serogroups C, Y & W13 in one study,
however, the seroconversion rates obtained for serogroup A was between 90-97% which meet the specifications of
WHO. Therefore, the vaccine can benefit this age group from only serogroupAN. meningitides.
Q: Does thevaccine offer a completeprotection against harvesting the disease, what other risks should he encountered?
A: Although the vaccine can offer protection against the infection, it doesn't prevent the acquisition of the pharyngeal
carriage of the organism. People returning from the pilgrimage may spread the bacteria to their unvaccinated household
contacts or even to the community in large. In addition to the vaccine, chemoprophylaxis is needed to eliminate the risk
of N. meningitides nasal and pharyngeal caniage. Recommended regimens include : adults: Ciprofloxacin 500mg
single dose, Pediatrics: Rifampin: lOmgkg PO q12 hrs for 4 doses (5 mgkg for infants less than 1month), Pregnant:
Ceftriaxone: 250 mg IM side dose.
Q: Does the vaccine interact in a negative way with other kind of vaccines or drugs ?
A: Giving the vaccine to patients on immunospressive medications may not produce adequate seroconversion to the
bactericidal antibody titer. MencevaxCO can be administered at the sametime as other vaccines.
Pharmacy Update, Volume 12, No. 4
5s: Mark UD vour
Pharmacy: A W e m i o n in Transition
19th 20thApri1, 2005
Laryngeal and Tracheal Surgery
International Symposium
8th 10th February, 2005
The crossroad of Biotechnology
9th 10th Febmary, 2005
Fourth International PCNE
Working Conference.
l Care Research:
Beyond the pharmacy perspective
16th 20th February, 2005
106thAnnual Meeting of
American Society for Clinical
Pharmacology and Therapeutics
2nd - 5th March, 2005
2005 European Association of
Faculties of Pharmacy
9th - 12th March, 2005
King Faisal Specialist Hospital
&Research Center, Riyadh,
Saudi Arabia
King Faisal Specialist Hospital
& Research Center, Riyadh,
Saudi Arabia
Biotechnology Research Institute NRC, Montreal, Canada.
Pharmakon Danish College of
Pharmacy Practice, H i l l e d , Denmark
Walt Disney World Swan and
Dolphin Hotel, Orlando, Florida, USA
Le Meridien Phoenicia, Floriana,
h t m ' l h n m
NEW STAFF: Welcome aboa
Mr. Mohammed Al-Jamal
1st Lt. Khalid Al-Otaibi
1st Lt. Mohammed AI-H
Dr. Mohammed Al-Sult;
Mr. Majed Al-Afraa
Mr. Abdulkarim Al-Mutairi
C l ~ n ~ cPharmacy
Clinical Pharmacy
On site training
On site training
Clinical Pharmacy
On site training
.Patient Pharmac!
IS: congrr
Major. Mazen Al-Omran
Mr. Abdulaziz Ibn Al-Shiekb
Major. Sultnn Al-A
Clinical pharmacist
Clinical pharmacist
DUE specialist
OJT pharmacist
umacy Techniciru
From OJT to a pharmacist
' '
Ms. Fadwa Al-Khuraisy
KH R~s~der
SCFlvIS Joint Risidenc
SCFMS Joint Risidenc
ContributineEdiloc Mr. AbduUah A1 Mehaisen, Assistant Director of Medica1Adminisb~'onfor Pharmacy Affairs.
Publishine Contributor: Jawssem-CiIag Pharmacenliccrls, Riyadh, Saudi Arabia
Address and correswndcnce: Editors, Phcvntaey Up*, Depameni of Phannaey, Riyadh Anned Forces
Hospital, R0.Box 7897,Rigrullr, 11159, Kingdom of Saudi Arabia
Telephone: 477-7714, X=S243
P h a m a q Update, Yolurne 12, No.4