L L P r n -a UPDATE A Riyadh-Armed-Forces*Hospital.(RKH)- 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 I ".1 d INTRODUCTION 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 . &bachialresistmu 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, - I * is I " I A d Pharmacy Upc*r!e, Volume 12, No. 4 -I I":'""l": 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 4 ou can contact the InfectiousDiseases team r clinical services at the pharmacy epartmentfor pn~r-ssistance. - ONCE DAILY.DOSING (ODD): $%tie& n&sBigtbb 4 Eridocartlitis , ,4 ~ ~ ~ ~ Y 4 CNS ipfedion J ESRD . ~ ~ ~ ~ B~,.,, Ascitis 4 * 4 Pregnancy 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). ~ j i t 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 adjustment. Failure to adhere to monitoring guideline, the lab will cancel the request. * Target range: - Trough (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 prnoUL 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 Aminoglycosides 2rCI (mllmin) > 80 I 60-80 1. Calculate Ideal Body Weight (IBW) 40-59 Dose (melkd I24 h As above If TBW less than IBW then use TBW. For obese patients use the adjusted body weight (ABW): 4. Serum concentration monitoring: b Request justifications( i.e. is the patient b b b W 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 days. 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 medical condition affecting Use I B W unless the patient is underweight 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 mw. U% D 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 request. Target level is: [)rug * - I I Tt.ough Peak Doses: Gentamicin 3 mg 1 kg (IBW) every 8 hrs & Netilmicin 3.5 mg 1 kg (IBW) every 8hrs for patients with cysticfibrosis. 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: * * - b > > * * Request justifications (i.e. is the patient on dialysis, renal failure, ODD, C.D. Etc). Sampling within lab working hours 7:30 A.M. - 4:30P.M. Saturday - Wednesday. Duration of treatment greeter than 3 days. 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 adjustment. 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 Aislvaia. ** 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 D b 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 ICAWCAvHD\: 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 rmac 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 al (AMI) 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 l ~ n s h t (NcI) e 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. a 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, hvaotonia, hvaoreflexia andresviratorv difficulties. .. . .A b b An infant with botulism is often diagnosed with sepsis or meningo-encephalities.Dehydration Pharmacy U$ate, Volume 12, No. 4 I 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: A. GENERAL: 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. C.ANTIBIOTICS: 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 botulism. .. I m ~ o r t a nNotes t The prognosis is excellent, with a case- fatality rate oflessthan2%. 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. . I 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 I 1I a rn '- - 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. P a 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 http:/lwww.kfshrc.edu.sa/symposia ihtmVpharmacymtml King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia http:llwww.kfshrc.edu.sa/symposia Biotechnology Research Institute NRC, Montreal, Canada. Http://www.pcne.org/dokumenter/first announcementO5.pdf - Pharmakon Danish College of Pharmacy Practice, H i l l e d , Denmark httD:Nwww.~cue.oreldokumenter/first mbun~em~en~5.~df Walt Disney World Swan and Dolphin Hotel, Orlando, Florida, USA http://www.ascpt.org/muaV Le Meridien Phoenicia, Floriana, Malta h t m ' l h n m ~~lm.edu.mt/phcy/activities.htm NEW STAFF: Welcome aboa Mr. Mohammed Al-Jamal 1st Lt. Khalid Al-Otaibi 1st Lt. Mohammed AI-H I Dr. Mohammed Al-Sult; Mr. Majed Al-Afraa Mr. Abdulkarim Al-Mutairi C l ~ n ~ cPharmacy al Clinical Pharmacy On site training On site training Clinical Pharmacy On site training .Patient Pharmac! - IS: congrr I= Major. Mazen Al-Omran Mr. Abdulaziz Ibn Al-Shiekb Major. Sultnn Al-A Clinical pharmacist Clinical pharmacist Pharmacist Pharmacist DUE specialist OJT pharmacist umacy Techniciru - Pharmaceut~calServ~cesCoordmnator From OJT to a pharmacist I___ ' ' Ms. Fadwa Al-Khuraisy KH R~s~der aCHR38iIh SCFlvIS Joint Risidenc SCFMS Joint Risidenc = B 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 m