Toxi Drug Info
September 2009
Event Update
Volume 3
Issue 3
2
Generic Drugs Policy
Watch out
3
Medication Safety Alerts
Toxi-Review
7
Organophosphorous
Extemporaneous
8
Tacrolimus In Oral Suspension
Question of the
month
9
Oral Hypoglycemic Agents
During Pregnancy
Pharmacovigilance
11
Minimizing Adverse Drug Events
In Elderly
Review
13
Electronic Prescribing, Benefits
Versus Risks
Medication Safety
15
Insulin Glargine & Cancer
Toxicology Quiz
16
Rumors vs Truth
17
HAAD Formulary
Update
18
News Update
19
Safety information on
Tamiflu® & Relenza® for
influenza A H1N1
‫ األدويـة و المنتجـات الطبيـة‬/‫إدارة الصيدلة‬
p d i c . h a a d . a e
Pharma/Medicines & Medical
Products Department
NEWS UPDATE
Health Authority - Abu Dhabi, Pharma/Medicines & Medical Products Department (PHM)
Chief editor
Dr. Abdullah Hassan, Manager, PHM
Executive Editors
Dr. Mohammed Abuelkhair, Head, Drugs & Medical
Products Regulation Section, PHM
Dr. Yasser Sharif, Head, Medications & Medical
Products Safety Section, PHM
Contributing Authors
Dr. Shajahan Abdu, Pharmacovigilance Officer
(Generic Drugs: From Policy To Implementation)
Dr. Kefah Al Qawasme, PDIC Officer
(Medication Safety Alerts)
Dr. Yasser Sharif, Head, Medication & Medical
Products Safety Section & Dr. Sherif El Ghandour,
PDIC Officer (Organophosphorous Poisoning Review)
Dr. Sherif El Ghandour, PDIC Officer (Is The Use Of Oral
Hypoglycemic Agents Contraindicated During Pregnancy?)
Dr. Maysoon Saffarini, PDIC Officer
(Tacrolimus In Oral Suspension Form)
Dr. Sahar Fahmy, Pharmacovigilance Officer
(Minimizing Adverse Drug Events in Elderly)
Dr. Majdoline Abu Musallem, Import and Export Regulation Officer
(Electronic Prescribing, Benefits Versus Risks)
Dr. Hadaya Gharibyar, PDIC Officer (Insulin Glargine (LANTUS®)
and Cancer Association: A Closer Look at the Literature)
Dr. Rania Al Dwiek, PDIC Officer (Rumors Versus Truth)
Acknowledgment
We thank Dr. Kefah Al Qawasme for actively participating in
producing this issue.
We value your comments. Please provide us with your feedback regarding the contents by reaching us at:
pdic.haad.ae
Poison & Drug Information Center
Mission
l
l
To enhance the level of pharmaceutical care through enabling Physicians, Pharmacists, Nurses and other members
of the healthcare team, to access accurate and relevant poison and drug information.
To protect the health of community by providing immediate,
uninterrupted, high quality emergency telephone advice for
poison exposures and to serve as the primary resource for
poison education, prevention and treatment in Abu Dhabi.
Vision
l
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Serve our community and healthcare professionals by providing health information and medical expertise regarding
poisonings, drug information and adverse drug events.
Conduct research on the prevention and treatment of toxicity.
Provide accessible, reliable and responsive services through
state-of-the-art information technology systems.
Values
Excellence, Integrity, Innovation, Collaboration- and Leadership. We embody these qualities in our commitment to enable
accessible healthcare for all.
The PDIC serves all UAE healthcare facilities and its medical
and healthcare staff. It also serves and receives inquiries from
the general public nationwide
Poison and Drug Information Center
Services
1. Poison management and prevention
l
PDIC will assist the healthcare professionals and general
public with poison emergencies by providing quick and accurate information in regard to the following:
l Signs and symptoms of toxic exposures to specific poisons
l Overdoses with medications
l Exposure to household chemicals, cosmetics,.etc.
l Herbals, traditional medicines and dietary supplements
l Industrial chemicals and exposure
l Bites and stings from venomous creatures
l Toxic plants
l
l
l
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First aid advice on management of toxic exposure
Advice on detailed medical management of poisonings
Antidotes uses and availability
Poison prevention
2.Safe Use of Medications
PDIC plays an important role in promoting medication safety
through
l Dissemination of information on the latest recommendations
regarding safe medication use to all health care professionals
l Tracing and follow up medication errors, adverse drug
events and side effects, circulates the relevant findings and
recommendations to all medical and health care staff.
l Follow up on adverse effects of herbal and health supplements
3.Educational and Services Program
PDIC is an educational and service center designed to support
poison and drug information provided to the public and health
care professionals in regard to the following areas:
l Education of the public in the areas of poisoning prevention
and first aid.
l Education of health care professionals in the areas of clinical toxicology, poisoning epidemiology, poisoning prevention, toxicological diagnosis and care.
l Provision of drug information to practitioners, patients and
their families and other personnel (students, faculty teachers, universities) to optimize medication use and achieve
specific health outcomes.
4.HAAD Medications Formulary
PDIC continuously strives for improved patient safety, appropriate use of medications and improved access to pharmaceuticals through its active participation in Formulary Committee.
PDIC supports the Formulary Committee through:
l Evaluating new medication
l Developing therapeutic guidelines
l Updating professionals on new labeling of established products
5. Coordination of Drug Research and Promoting
Research on Medication Use
The center supports in the review of pharmaceutical clinical research protocol, as an active participant in the investigation review board. As part of its responsibility, the center keeps track
of pharmaceutical clinical research at health care facilities by
coordinating and conducting research regarding:
l Drug pricing, affordability, accessibility and availability of
medication
l Analysis of pharmacoeconomic studies and their relevance
to the community
l Situational analysis of drug use problems.
l Prescribing patterns
EVENT UPDATE
GENERIC DRUGS:
FROM POLICY TO IMPLEMENTATION
Introduction
G
eneric Drugs have existed throughout the history of
the pharmaceutical industry, but modern generic firms
emerged only in the mid 1960s in the context of the shakeup
of regulatory arrangements in USA following the thalidomide
tragedy. The 1984 US Drug Price Competition and Patent
Restoration (Hatch-Waxman) Act was the decisive moment in
the development of the generics industry in the world’s major
pharmaceutical market. The Hatch-Waxman Act provided for
facilitated market entry for generic versions of all post-1962
approved products, in exchange for an extension of the patent
period (Congressional Budget Office 1998). This opened the
floodgates for generic competition of pharmaceutical products,
creating the modern generic pharmaceutical industry.
However, it took until the 1990s for generic competition to alter significantly the dynamics of the US pharmaceutical market. A key driver was the spearheading by Health Maintenance
Organizations and Pharmaceutical Benefit Management companies of cost containment measures such as generic prescribing, brand substitution by pharmacists, and reimbursement
on the basis of the cheapest brand. By 1997, 63% of Health
Maintenance Organizations are said to have imposed mandatory generic substitution.1 The Waxman-Hatch Act is estimated
by the Congressional Budget Office to have saved consumers
US$ 8-10 billion in 1994, and presumably at least as much in
subsequent years.2
The World Health Organization and pharmaceutical experts have
recommended that Generic Drug Policies be implemented to
improve the availability of affordable medicines, as it is one of
the most visible indicators of quality health services.3 However,
policy in this area is fraught with contention that arises inescapably from the fact that generic drugs invite cost effective comparisons and make substitution possible. On one hand, generic
competition is seen as a cost containment, and as also a way of
adding to innovative pressures on originator firms. The opposing
perspective is to consider the growth of Generics as opposing to
the growth of research based industry and Generic substitution
and related measures as an intrusion on the professional authority of doctors.
HAAD Initiatives
Health Authority Abu Dhabi (HAAD) introduced ‘Unified Prescription Form’ and mandated Generic prescribing in March
20094, as part of the ongoing efforts to improve the prescribing practices in the Emirate of Abu Dhabi. The comprehensive
generic drugs policy, published in August 2009, provided for
additional strengthening of controls over the generic prescribing and dispensing practices, ensuring that patients have access to affordable and quality medicines appropriate to their
clinical needs.
HAAD Pharma / Medicines and Medical Products Department
also organized 4 workshops in August 2009 to educate the
stakeholders on the new Generic Drug Policy. The workshops
were held at HAAD auditorium and specifically targeted
pharmacists, physicians & allied health care professionals,
insurance companies, pharma industries and drug agents.
Generic Drugs Policy5
HAAD Generic Drug Policy is well balanced and applies to
pharmacists, all other healthcare professionals who have the
authority to prescribe drugs (physicians), and healthcare
providers in whose facilities such pharmacists or physicians
are employed.
Key features:
Duties on Physicians
Physicians must prescribe the medication for a patient in the
standard prescription format (developed by HAAD) and must
refer to the medication in its Generic Name (active Pharmaceutical
ingredient) unless one of the exceptions set out below applies.
Exceptions:
1. A physician who prescribes a medication for a patient may
choose not to prescribe the medication by reference to its
Generic Name where that medication is:
(a)a drug registered with the Federal Ministry of Health as
an ‘over-the-counter’ drug or ‘general sale product’,
(b)a dietary supplement or food supplement,
(c)a herbal or homeopathic remedy,
(d)a vaccine or insulin preparation, or
(e)Narrow Therapeutic Range Drugs (Refer Appendix B of
HAAD Generic Drugs Policy)
2. A physician who prescribes a medication for a patient may
also choose not to prescribe the medication by reference to
its Generic Name, where to do so would place that patient’s
health at risk because the patient:
(a)has a documented history of an allergic or other adverse
reaction to a particular Generic Drug, or
(b)has previously suffered unsuccessful therapeutic control
with a Generic Drug.
In such an instance, the physicians must l also write the phrase ‘Do Not Substitute’ or the initials
‘DNS’ next to item prescribed,
l document the reasons for prescribing a brand-name drug in
the patient record, and
l be able to give the reasons for prescribing a brand-name
drug, if requested to do so by HAAD.
Toxi-Drug Info - Sept. 2009 - Volume 3 - Issue 3
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Duties on Pharmacists
1. The pharmacist must review a patient’s medication on each
occasion before dispensing it to the patient.
2. May usually (subject to certain exceptions) substitute
appropriate generic drugs for brand-name drugs.
3. Must not dispense a generic drug in place of a prescribed
brand-name drug where the prescribing physician has
placed the phrase ‘Do Not Substitute’ or the initials ‘DNS’
next to the name of the item being prescribed.
4. Must not engage in the therapeutic substitution of drugs (e.g. replace
ranitidine for cimetidine or ofloxacin for ciprofloxacin, etc.)
5. In dispensing to patients on long term therapy:
(a)be consistent over time in the selection of generic drugs
that are dispensed, and
(b)where it is necessary to dispense a Generic Drug under a
different brand name to that of the same generic drug which
was previously dispensed to the patient, explain to the
patient that the medication remains the same in substance.
The Duty on Healthcare Providers
Each healthcare provider must ensure that healthcare
professionals employed by it at their healthcare facilities
comply with any duties placed on them under this Policy.
Request for Exemption from Generic Prescribing
Physicians may submit a request to HAAD, if they consider that
a particular drug/drug molecule (other than those exempted
by HAAD), needs to be permanently exempted from generic
prescribing. All requests in this regard should be made only
through the ‘Exemption Request Form’6, and submitted directly
to HAAD Pharma/Medicines and Medical Products Department
or through email or fax (see contact details below).
A committee comprised of experts from ‘Pharma/Medicines and
Medical Products Department’ and ‘Pharmacy and Therapeutic
Committee’ at HAAD will scientifically review the physician’s
request for exemption. If the committee recommends the drug
for exemption from generic prescribing, it will be communicated
to all healthcare professionals through HAAD health advisory
and /or circular.
For more information on generic prescribing or Generic
Drugs Policy, please contact:
HAAD Pharma/Medicines and Medical Products Department
Pharmacovigilance Center
Phone: 02 4193 348, 580 586. Fax: 02 4496679, Email: pv@haad.ae
References:
1. Mrazek M., Mossialos E. Increasing demand while decreasing costs of generic
medicines, The Lancet 2000;356(9244):1784-85
2. Congressional Budget Office 1998, p. ix.
3. Bulletin of the World Health Organization | January 2005, 83 (1)
4. HAAD CEO circular no (03/09)to all public and private sector hospitals.
5. HAAD Generics Drug Policy PHP/PHM/P0003/09, Date of Approval: August,
2009. Also available at http://www.haad.ae/haad/tabid/82/Default.aspx.
6. HAAD Generic Drugs Policy, PHP/PHM/P0003/09, Appendix C.
MEDICATION SAFETY ALERTS
Safety information on oseltamivir
(Tamiflu®) and zanamivir (Relenza®)
for pandemic swine influenza A H1N1
D
uring August 2009, the Medicines and Health Care
products Regulatory Agency (MHRA) at the UK posted
on their website the information below concerning the safety
of oseltamivir and zanamivir. Tamiflu and Relenza are
both neuraminidase enzyme inhibitors. They act by inhibiting
entry of influenza virus into uninfected cells and preventing
the release of recently formed virus particles from infected
cells. Tamiflu is given orally (capsules and solution) and
Relenza is given by inhalation (Diskhaler system). Both
have substantial experience of use and favorable benefit-risk
profiles.
Tamiflu®
Side effect profile
The most common side effects of Tamiflu are nausea,
vomiting, diarrhoea, abdominal pain, and headache. These may
usually occur after the first dose and will usually stop as treatment
continues. The frequency of these effects is reduced if Tamiflu
is taken with food. More serious side effects are very rare.
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Toxi-Drug Info - Sept. 2009 - Volume 3 - Issue 3
The product information for Tamiflu lists neuropsychiatric
disorders (reports of convulsions and delirium) in the side-effects
section. These events were added to the product information
as a precautionary measure. A causal association between
Tamiflu and the reported events has not been established.
Drug interactions
Clinically important drug interactions with Tamiflu are unlikely, including those involving competition for renal tubular secretion. However, care should be taken when prescribing Tamiflu
for patients who are taking co-excreted medicines with a narrow
therapeutic margin (eg, chlorpropamide or methotrexate).
No dose adjustment is required when coadministering with
probenecid in patients with normal renal function. Coadministration of probenecid, a potent inhibitor of the anionic pathway
of renal tubular secretion, results in an approximate two-fold
increase in exposure to the active metabolite of oseltamivir.
Renal impairment
Dose adjustment is recommended for adults with severe renal
insufficiency (creatinine clearance ≤ 30 mL/min).
Tamiflu is not recommended for patients with a creatinine
clearance of ≤ 10 mL/min or in those undergoing dialysis.
Watch Out
Relenza®
Relenza is delivered by inhalation using a Diskhaler. It has
been recommended for anyone with a kidney disorder or who
may be pregnant.
Reference:
1. UK Medicines and Health Care products Regulatory Agency (MHRA). On line
through: http://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/
CON054505. Accessed date: August 16th, 2009
Side effects
Tumor Necrosis Factor (TNF)
Recognized side effects to Relenza are very rare, but may include allergic-type reactions such as swelling of the face, mouth, or
throat; skin rash; or hives. Acute bronchospasm or serious decline in
respiratory function (or both) have been seen in patients with a history of asthma or chronic obstructive pulmonary disease (COPD),
and in those without a history of respiratory disease (see below).
Blockers (marketed as Remicade®,
Enbrel® and Humira®) and Cancer
The product information for Relenza also lists neuropsychiatric
disorders as a possible side effect of the medicine. As with Tamiflu,
these events were added to the product information as a precautionary
measure and a causal association with Relenza is uncertain.
Patients with asthma or COPD
Patients with severe asthma should not receive Relenza unless close medical monitoring and appropriate clinical facilities
are available to prevent bronchoconstriction. In patients with
persistent asthma or severe COPD, management of the underlying disease should be optimised during Relenza treatment.
How To Report Suspected Adverse Reactions From
Tamiflu® and Relenza®
Please report all suspected ADRs to Tamiflu and
Relenza to HAAD Pharma /Medicines and Medical
Products Department/ Pharmacovigilance Center by
any of the following: Phone: 02 4193 348, 580 586.
Fax: 02 4496679. Email: pv@haad.ae
l Please remember to include the following important information in your report:
- Patient age
- Indication (prophylaxis or treatment)
- Outcome of the ADR
- Information on any underlying risk factors for the
ADR or for influenza complications. Also mention if
there are no known risk factors
- Any other information about the patient or additional
clinical details that will help us in our assessment of
the case
l When influenza A H1N1 vaccines become available,
the Pharmacovigilance Center should also be contacted
to report suspected ADRs to these vaccines
Before this influenza A H1N1 outbreak, use of these medicines in the UAE and worldwide was limited. It is possible that the wider prescribing of these medicines in a
pandemic situation may reveal rare effects that have not
previously been reported. Therefore, it is important that
suspected ADRs to Tamiflu and Relenza are reported to us. If you suspect that a patient has experienced an
adverse reaction to these antivirals, please report as outlined above.
l
O
n August 4th 2009, US Food & Drug Administration (FDA)
notified healthcare professionals that it has completed its
assessment of tumor necrosis factor (TNF) blockers and has
concluded that there is an increased risk of lymphoma and
other cancers associated with the use of these drugs in children
and adolescents. This new safety information is now being
added to the Boxed Warning for these products. FDA has also
identified new safety information related to the occurrence
of leukemia and new-onset psoriasis in patients treated with
TNF blockers. The current prescribing information for TNF
blockers does contain a warning for malignancies, but does not
specifically mention leukemia. FDA is also requiring updates
to the current Medication Guide to help patients understand
the risks associated with TNF blocker therapy. TNF blockers
are approved for the treatment of one or more of a number of
immune system diseases including juvenile idiopathic arthritis
(JIA), rheumatoid arthritis, psoriatic arthritis, plaque psoriasis,
Crohn’s disease, and ankylosing spondylitis.
Recommendations for Healthcare Professionals:
Discuss with patients and families the increased risk
of developing cancer in children and adolescents, taking into account the clinical utility of TNF blockers, the
risks/benefits of other immunosuppressive therapies,
and the risks associated with untreated illness.
l Be aware of the possibility and monitor for the emergence of malignancies during and after treatment with
TNF blockers.
l Be aware of the possibility and monitor for the emergence or worsening of psoriasis during treatment with
TNF blockers, particularly pustular and palmoplantar
forms of psoriasis.
l Understand that some immune-related diseases, such as
Crohn’s, have been shown to increase cancer risk independent of treatment with TNF blockers while for others,
such as juvenile idiopathic arthritis (JIA), it is unknown
whether there is an increased cancer risk.
l Inform patients, their families, and caregivers of the
signs and symptoms of malignancies or psoriasis so they
are aware of and able to notify their healthcare professional of any unusual signs or symptoms.
l
Reference:
1. The US Food and drug Administration MEDWATCH. Safety Information and
Adverse Event Reporting Program. On line through: http://www.fda.gov/Safety/
MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm175843.
htm. Accessed date: August 16th, 2009.
Toxi-Drug Info - Sept. 2009 - Volume 3 - Issue 3
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Onabotulinumtoxin A (marketed
as Botox®/Botox Cosmetic®),
Abobotulinumtoxin A (marketed as
Dysport®)
O
n July 31, 2009, US Food & Drug Administration (FDA)
approved the following revisions to the prescribing information of Botox/Botox Cosmetic based on a safety
evaluation of the botulinum toxin products:
l A Boxed Warning highlighting the possibility of experiencing potentially life-threatening distant spread of toxin
effect from the injection site after local injection.
l Changes to the established drug names to reinforce individual potencies and prevent medication errors. The potency
units are specific to each botulinum toxin product, and the
doses or units of biological activity cannot be compared or
converted from one product to any other botulinum toxin
product. The new established names reinforce these differences and the lack of interchangeability among products.
The other botulinum toxin product in this class, AbobotulinumtoxinA (marketed as Dysport), was approved on April 29,
2009 and included the Boxed Warning, REMS, and new established name at the time of approval in the US.
Table 1 lists the established name changes and the approved
indications for each product.
Recommendations for Healthcare Professionals:
l
Be aware that a Boxed Warning has been added to the
prescribing information to highlight that botulinum
toxin may spread from the area of injection to produce
symptoms consistent with botulism. Symptoms such
as unexpected loss of strength or muscle weakness,
hoarseness or trouble talking (dysphonia), trouble
saying words clearly (dysarthria), loss of bladder control, trouble breathing, trouble swallowing, double vision, blurred vision and drooping eyelids may occur.
Understand that swallowing and breathing difficulties
can be life-threatening and there have been reports of
deaths related to the effects of spread of botulinum
toxin.
l Be aware that children treated for spasticity are at greatest risk for these symptoms, but symptoms can also occur in adults treated for spasticity and other conditions.
l Be aware that cases of toxin spread have occurred at
botulinum toxin doses comparable to those used to treat
cervical dystonia and at lower doses.
l Be aware that no definitive serious adverse event reports of distant spread of toxin effect have been associated with dermatologic use of Botox/Botox Cosmetic at approved doses.
l Be aware that no definitive serious adverse event reports of distant spread of toxin effect have been associated with Botox for blepharospasm or for strabismus
at approved doses.
l Understand that the established drug names of the botulinum products have been changed to emphasize the
differing dose to potency ratios of these products.
l Understand that botulinum toxin products are not interchangeable.
l Be aware that all botulinum toxin products have a
Medication Guide and urge patients, their families, and
caregivers to review it carefully.
l Understand that clinical doses expressed in units are
not comparable from one botulinum toxin product to
the next. Units of one product cannot be converted into
units of another product.
l
Reference:
US Food and drug Administration MEDWATCH. Safety Information and Adverse
Event Reporting Program. On line through: http://www.fda.gov/Safety/MedWatch/
SafetyInformation SafetyAlertsforHumanMedicalProducts/ucm164255.htm. Accessed
date: August 16th, 2009
Table 1. Summary of FDA-Approved Botulinum Toxin Products
Trade Name*NEW Drug NameOLD Drug NameIndication
Botox OnabotulinumtoxinA
Botulinum toxin type A
Botox Cosmetic OnabotulinumtoxinA
Botulinum toxin type A
Dysport
AbobotulinumtoxinA
Botulinum toxin type A
Cervical dystonia,
Severe primary axillary hyperhidrosis,
Strabismus, Blepharospasm
Temporary improvement in the appearance
of moderate to severe glabellar lines
Cervical dystonia, Temporary improvement
in the appearance to moderate to severe
glabellar lines
Myobloc**
Cervical dystonia
RimabotulinumtoxinB
Botulinum toxin type B
* The marketed trade names and the product formulations have not changed.
** Not available in the UAE and not approved by the Ministry of Health.
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Toxi-Drug Info - Sept. 2009 - Volume 3 - Issue 3
Watch Out
Mycophenolate mofetil and pure
red cell aplasia
O
n June 2nd, 2009, ROCHE pharmaceutical issued a Dear
Healthcare Professional Letter on the association of Mycophenolate mofetil (CellCept) with pure red cell aplasia.
The information has been reviewed and endorsed by the European Medicines Agency’s (EMEA) Committee for Medicinal
Products for Human Use (CHMP). This letter is posted on the
UK Medicines and Health Care products Regulatory Agency
(MHRA) and the United States FDA official websites.Mycophenolate mofetil (CellCept) is an immunosuppressant
indicated in combination with ciclosporin and corticosteroids
for prophylaxis of acute transplant rejection in adults receiving
allogeneic renal, cardiac or hepatic transplants, and in children
and adolescents (age 2–18 years) receiving renal transplants.
Up to April 2009, 41 cases of pure red cell aplasia had been reported worldwide in association with mycophenolate mofetil.
Pure red cell aplasia is a type of anaemia in which there is a selective reduction of red blood cell precursors on bone-marrow
examination. Some patients were also receiving other medicines that could have contributed to the development of pure
red cell aplasia (eg, alemtuzumab, tacrolimus, azathioprine,
and co-trimoxazole). In four cases dose reduction, and in 12
cases discontinuation, of mycophenolate mofetil led to resolution of the condition. The mechanism by which mycophenolate
mofetil may cause pure red cell aplasia is unknown.
Recommendations for Healthcare Professionals:
l
Dose reduction or discontinuation of mycophenolate
mofetil should be considered in patients who develop
pure red cell aplasia. Changes to treatment should be
done only under specialist supervision to minimize the
risk of graft rejection
2. US Food and drug Administration MEDWATCH. Safety Information and Adverse
Event Reporting Program. On line through: http://www.fda.gov/Safety/MedWatch/
SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm177397.htm.
Accessed date: August 16th, 2009
Leukotriene Inhibitors:
Montelukast
O
n August 28th, 2009, US Food & Drug Administration (FDA) provided healthcare professionals with
updated information on the original March 2008 early
communication and January 2009 follow-up communication about the ongoing safety review for the leukotriene inhibitors, montelukast. Neuropsychiatric events
have been reported in some patients taking montelukast
(Singulair). FDA has requested that manufacturers
include a precaution in the drug prescribing information (drug labeling). The reported neuropsychiatric
events include postmarket cases of agitation, aggression, anxiousness, dream abnormalities and hallucinations, depression, insomnia, irritability, restlessness,
suicidal thinking and behavior (including suicide), and
tremor.
Recommendations for Healthcare Professionals:
l
l
l
Patients and healthcare professionals should be aware
of the potential for neuropsychiatric events with these
medications.
Patients should talk with their healthcare providers if
these events occur.
Healthcare professionals should consider discontinuing
these medications if patients develop neuropsychiatric
symptoms.
References:
Reference:
1. UK Medicines and Health Care products Regulatory Agency (MHRA). On line
through http://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/
CON051770. Accessed date: August 16th, 2009
1. FDA MedWatch. On line through: http://www.fda.gov/Drugs/DrugSafety/ PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm165489.htm. Accessed date: August 28th, 2009
Prescription Only Medications (POM)
Stop Dispensing without a prescription
Dispensing (POM) without
A prescription is illegal
UAE Federal Law No. 4; Article 11 for the year of 1983 about pharmaceutical
Professions and Institutions
“The licensed pharmacist should not give any medicine or medicinal
preparation without a medical prescription in a clear hand-writing carrying
the name of the licensed doctor who issued it, its stamp and date issued.”
Toxi-Drug Info - Sept. 2009 - Volume 3 - Issue 3
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eview
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Organophosphorous
Poisoning Review
Introduction:
Organophosphorous compounds (OPs), generally known as
cholinesterase inhibitors are widely used pesticides that may
cause poisoning after occupational, accidental or suicidal
exposure. Poisoning with OPs frequently causes ill-health that
may be severe enough to cause death, particularly in developing
countries. The number of intoxication cases with OPs is
estimated to be 3 millions each year. Fatality rates ranges from
15-20% and according to the WHO around 200,000 people die
each year from OPs pesticide poisoning.1
Mechanism of toxicity:
OPs primarily inhibit acetylcholinestrase enzyme (AChE) which
is found in synaptic junctions and red blood cells, it also inhibits
butyrylcholinestrase (psudocholinestrase) which is found in the
plasma. Inhibition of AChE leads to accumulation of acetyl choline
(Ach) at muscarinic receptors, nicotinc receptors and central nervous system, thereby, disturbing transmission at parasympathetic
nerve ending, sympathetic nerve endings, sympathetic ganglia, neuromuscular end- plates and certain central nervous system regions.2
Permanent inhibition of AChE may occur through covalent binding by the OP to the enzyme. This is known as “aging,” and its
rate of development is variable and depends on the specific OP.
Exposure:
OPs are absorbed by the following routes;
l Inhalation
l Ingestion
l Skin absorption
Clinical presentation:
Signs and symptoms of acute organophosphate poisoning may
occur almost immediately or be delayed several hours, depending on the above factors. Clinical manifestations may be classified into:
l Muscarinic manifestations include; vomiting, diarrhea, abdominal cramping, bronchospasm, miosis, bradycardia, and
excessive salivation and sweating. Fluid losses can lead to
systemic hypovolemia, resulting in shock.
l Nicotinic effects include muscle fasciculations, tremor, and
weakness. Respiratory muscle weakness complicated by
bronchorrhea may lead to respiratory arrest and death.
l Central nervous system (CNS) poisoning may cause agitation, seizures, and coma. Furthermore, delayed, often permanent peripheral neuropathy may occur.
l Two days after recovery from acute cholinergic crisis, some
patients may develop proximal muscle weakness that start as
neck weakness, progressing to proximal limb weakness and
cranial nerve palsies. Respiratory muscle weakness and respiratory arrest may occur abruptly. This is known as “the intermediate syndrome” which is thought to be caused by a redistribution of lipophilic pesticides or result from inadequate oxime
therapy. Symptoms may last for 2-4 weeks, and do not usually
respond to additional treatment with oximes or atropine.4
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Toxi-Drug Info - Sept. 2009 - Volume 3 - Issue 3
In addition, chemical pneumonitis may occur, if a product
containing a hydrocarbon solvent is aspirated into the lungs.2
Diagnosis:
Diagnosis is made on the basis of clinical suspicion, the characteristic
clinical signs, smell of pesticides or solvents, and reduced psudocholinestrase or AChE activity in the blood. However the latter diagnostic
assays are not readily available in time to affect the clinical decision.
Patients with severe OP poisoning typically present with pinpoint pupils, excessive sweating, reduced consciousness, and
poor respiration. The major differential diagnosis is carbamate poisoning, which is clinically indistinguishable, however
carbamates do not age AChE, and therefore toxicity is usually
brief and self limiting. In addition carbamates produce less pronounced CNS effects due to limited passage through the blood
brain barrier (BBB).1
Another differential diagnosis is heat stroke (especially among
farmers or insect fighters during the summer season);
The following table 1 summarizes differences between OP/ Carbamate poisoning and heat exhaustion signs and symptoms.
l
Table 1.Signs and symptoms of heat exhaustion versus
OP/ Carbamate
Heat ExhaustionOP / Carbamate
Nausea
Nausea and diarrhea
Dry membranes
Moist membranes
Dry mouth
Salivation
No tears
Tears
Fast pulse
Slow pulse
Dilated pupils
Small or pinpoint pupils
Decontamination
Healthcare professionals are at risk of poisoning during initial
stabilisation of patients poisoned with organophosphorus. There
are some case reports for such poisoning; fortunately none have
shown inhibition of acetylcholinesterase or butyrylcholinesterase
in health-care workers consistent with substantial exposure to
organophosphorus. Therefore, rescuers should wear chemicalprotective clothing and gloves when handling a grossly contaminated victim. If there is heavy liquid contamination with a
solvent such as xylene or toluene, clothing removal and victim
decontamination should be carried out outdoors or in a room with
high-flow ventilation. Guidelines also recommend universal precautions, maximum ventilation, and frequent rotation of staff, so
that effects of solvent and pesticide are kept to a minimum.5
Skin: remove all contaminated clothing and wash exposed
areas with soap and water.
Eyes: irrigate with generous amount of slightly warm water.
Ingestion: activated charcoal may be given with early presentation and when the patient is cooperating. Gastric lavage
should be done only after intubation.
Dialysis is of no value most of the times due to large volume of
distribution of OPs.
s
Extemporaneou
Treatment6
Treatment includes emergency and supportive treatment; secure
open airway, give oxygen, if intubation is required, use non- depolarizing agent such as atracurium or vecuronium. Give benzodiazepine for seizures, it also helps if patient is agitated.
Specific drugs and antidotes; Muscarinic antagonist (Atropine)
and AChE activator such as pralidoxime chloride.
Atropine dose:
If symptomatic patient, intravenous (IV) atropine should be
given until atropinization is achieved. For adults a dose of 2 to
5 mg; and for children a dose of 0.05 mg/kg is recommended. If
inadequate response, double the dose and repeat it every 10 to 20
minutes as needed to dry pulmonary secretions. Atropinization
may be required for hours to days depending on severity.
Despite of the controversy regarding the effectiveness of pralidoxime7,
it is recommended by the WHO guidelines and almost in all textbooks,
however there is no consensus on the optimum dose.
Pralidoxime Chloride dose:
WHO currently recommends an initial bolus of at least 30
milligrams/kilogram followed by an infusion of more than 8
milligrams/kilogram/hour.
Alternatively adults may receive 1 to 2 g pralidoxime in 100
milliliters of 0.9% saline to be infused over 15 to 30 min.
Follow by infusion of 500 mg to 1 g/hr as a 2.5% solution.
Alternatively, the initial dose may be repeated 1 hr and then
every 3 to 8 hr if muscle weakness or fasciculations persist
(continuous infusion is preferred).
Children may receive initially 20 to 50 mg/kg (max 2 g/dose)
infused over 30 minutes as a 5% solution in 0.9% saline, followed
by a continuous infusion of 10 to 20 mg/kg/hour. Alternatively,
repeat initial bolus dose in 1 hr and then every 3 to 8 hr if muscle
weakness or fasciculations persist (continuous infusion preferred).
References:
1. Michael Eddleston, N.A.B., Peter Eyer, Andrew H Dawson, Management of acute
organophosphorus pesticide poisoning. Lancet, 2008. 371: p. 597-607.
2. David A. Tanen, M., Poisoning & Drug Overdose, in Organophosphorus and
Carbamate Insecticides, K.R. Olson, Editor. 2006, McGraw-Hill.
3. WHO | The WHO Recommended Classification of Pesticides by Hazard. 2004.
4. Toxicology Secrets. The Secret Series, ed. C. Ling, Erikson, Trestrail 2001, Philadelphia: Hanley & Belfus, INC., Medical Publisher.
5. Little, M. and L. Murray, Consensus statement: Risk of nosocomial organophosphate poisoning in emergency departments. Emergency Medicine Australasia,
2004. 16(5/6): p. 456-458.
6. ORGANOPHOSPHATES in POISINDEX® Managements, in Thomson Healthcare. 2008, Thomson Reuters.
7. Bairy KL, V.S., Sharma Alok, Sammad V, Controversies in the management of organophosphate pesticide poisoning. Indian Journal of Pharmacology, 2007. 39(2):
p. 71-74.
Tacrolimus in oral suspension form
Tacrolimus (Prograf®) is a drug that suppresses the immune system and is used to prevent rejection of transplanted
organs. It accomplishes its’ immune-suppressing effect by inhibiting an enzyme (calcineurin) crucial for the multiplication
of T-cells, cells that are vital to the immune process. The use
of oral tacrolimus allows transplantation specialists to reduce
the dose of steroids which are also used to prevent rejection.
This “steroid-sparing effect” is important because of the many
side effects that can occur when larger doses of steroids are
used for a long period of time. Tacrolimus was approved by
the FDA in April, 1994 for liver transplantation and also has
been used in patients for heart, kidney, small bowel, and bone
marrow transplantation.1
Tacrolimus suspension is used in most paediatric hospitals
and can be compounded at a concentration of 0.5 mg/mL.
The existing 0.5mg/mL suspension has a two-month expiry
date, requiring frequent manufacture.2
Because of the potential risk of toxicity, it is prudent to avoid
unnecessary exposure through either skin contact or inhalation of dust. Precautionary measures such as using a fume (or
vertical-laminar-airflow) hood and wearing latex gloves are
recommended. If a fume hood is not available, it is advised
to wear a surgical mask while at the same time minimizing
the creation of dust.4
Table 1 is one method for the preparation of Tacrolimus
suspension at a concentration of 0.5 mg/ml. 3,4
Table 1. Ingredients
Tacrolimus (capsules)
-----------------
25 mg
Ora-Plus suspending agent
-----------------
25 mL
®
Simple Syrup, NF
QSAD ------------- 50 mL
Final concentration = 0.5 mg/mL
Method
1. Empty the contents of five 5mg Prograf® capsules into
a glass mortar and work to a smooth paste with a small portion of the Ora-Plus® suspending agent.
2. Add Ora-Plus® gradually and mix well until all the 25
mL of Ora-Plus® are added.
3. Add about 25 mL of Simple Syrup NF to bring the total
volume of the suspension to 50 mL
4. Mix well and transfer to an amber polyethylene terephthalate glycol (PETG) bottle.
5. Label the bottle “Shake Well Before Using” and “Use Cytotoxic Drug Precautions.”
6. Label with an expiration date of 50 days.
References:
1. “TACROLIMUS-ORAL Index “ through online :http://www.medicinenet.com/
tacrolimus-oral/article.htm , Accessed on 27th August ,2009
2. Australian Resource Centre for Healthcare Innovations (ARCHI) , http://www.
archi.net.au/e-library/safety/tacrolimus , Accessed on 27th August ,2009
3. Tacrolimus Extemporaneously Prepared, http://www.umm.edu/altmed/drugs/
tacrolimus-121250.htm , Accessed on 27th August ,2009
4. Extemporaneous Preparations , http://the Drug Monitor - Extemporaneous
Preparations - Nasr Anaizi, PhD.mht , Accessed on 27th August ,2009
Toxi-Drug Info - Sept. 2009 - Volume 3 - Issue 3
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Is the use of Oral hypoglycemic agents
contraindicated during pregnancy?
I
nsulin use during pregnancy is preferred over oral hypoglycemic agents (OHAs) based on the perceived idea that
insulin does not cross the placenta. However OHAs cross the
placenta causing stimulation of the fetus pancreas leading to
hypoglycemia.1 Furthermore, early reports of increased mortality with the use of some OHAs compared with insulin discouraged the use of OHAs in the management of gestational
diabetes.2
Recent studies have shown that not all OHAs cross the placenta equally. While some of them cross freely, others cross
minimally.
Sulfonylureas
In one experimental study, four members of sulfonylureas were
tested for placental transfer using the human placental cotyledon
perfusion model. The investigators found that tolbutamide and
chlorpropamide more readily pass the placenta (21.5% and
11% respectively) than glyburide (glibenclamide) and glipizide
(3.9% and 6.6%) respectively.3 Evidence from another study
showed that glibenclamide does not cross the placenta. The
study in which serum cord blood in 12 pregnant women was
tested for the presence of glibenclamide, the women were
taking glibenclamide with average dose of 9 mg/day, although
the drug was detected in the maternal serum, it was not detected
in the serum cord blood. The absence of glibenclamide at the
serum cord blood was explained by the author to be due to
the high protein binding of glibenclamide (99.8%) and its short
elimination half life 10 hours.4
Metformin has been shown to pass freely across the placenta.5
Two in vivo studies measured maternal and cord blood samples
in women taking metformin throughout pregnancy (850 mg twice
daily in 15 women and 2000 mg/day in 8 women). The results of
these trials showed that the fetus is exposed to concentrations as
high as or higher than those seen in the maternal circulation.5’6
The relatively new class, thiazolidinedione was also found to
cross the placenta during the first trimester in one study. The study
included 31 women who were undergoing surgical terminations
at 8-12 weeks of gestation; all women were given two 4 mg doses
of rosiglitazone. Analysis of fetal tissue, coelomic fluid, and
amniotic fluid revealed that rosiglitazone crossed the placenta in
all women, especially in those over 10 weeks’ gestation7.
OHAs during first trimester
The safety of glibenclamide at doses 5-20 mg daily and metformin
at doses 1.5-3g daily during the first trimester was studied in several small cohort studies, only two of them showed an increased
rate of congenital anomalies compared with women taking insulin.
However, these two studies were small (20 and 43) respectively;
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Toxi-Drug Info - Sept. 2009 - Volume 3 - Issue 3
women did not have ideal glycemic control and a regression analysis was not performed in either study to control for glycemic control.5 Sulfonylureas were not found to be associated with congenital anomalies in another well controlled study. The study included
women with type 2 diabetes mellitus who were treated with diet
therapy, exogenous insulin, or sulfonylurea compounds during the
first 8 weeks of gestation. Assessment of all the delivered infants
(332) in this study showed no effect for the treatment modality on
the rates of both major and minor anomalies. These results lead
to the conclusion that the risk in individual patients appears to be
related to maternal glycemic control rather than to the mode of
antidiabetic therapy during early pregnancy.8
In one study, metformin (2.55 g/day) was used to facilitate conception in 72 oligoamenorrhoeic women with polycystic ovary
syndrome (PCOS). In the 63 live births, there was no difference between them and the normal neonatal population at the
primary outcomes. Metformin therapy was safely associated
with reduction in first trimester spontaneous abortion and in
gestational diabetes, was not teratogenic, and did not adversely
affect birth-weight or height and motor and social development
at 3 and 6 months of life.9
In another retrospective study, sixty-five women with polycystic ovary who received metformin and became pregnant during
treatment were compared with 31 women who did not receive
metformin (control group). The early pregnancy loss rate in
the metformin group was significantly lower than the control
group (P < 0.001). In the metformin group, 62 pregnancies resulted in live births. Of these, 53 were term deliveries and 8
were preterm (<37 wk). All babies were normal neonates with
appropriate size for gestational age. Only one baby, delivered
at term, demonstrated a fetal abnormality (achondrodysplasia).
In the control group, 18 pregnancies resulted in live births. Of
these, 12 were term deliveries and 6 were preterm. No fetal
abnormalities occurred in the placebo group.10
The published data on the use of thiazolidindione during the
first trimester is sparse, a case report described a 25-year-old
woman with PCOS who took rosiglitazone 4 mg/day for the
first 4 weeks of the pregnancy and delivered a healthy infant.11
All the above data about the use of OHAs during the first trimester are not from randomized controlled trials (RCT); a more
robust data from properly conducted randomized controlled
clinical trials are warranted, however, it appears that both sulfonylureas and metformin have low risk for teratogenecity.
OHAs during second and third trimesters
Glibenclamide use during the second and third trimesters was
studied in a randomized controlled trial (RCT) that included 404
women with gestational diabetes that required treatment. The
women were randomly assigned between 11 and 33 weeks of ges-
NTH
QUESTION OF THE MO
tation to receive glibenclamide or insulin. The primary end-point
was achievement of the desired level of glycemic control. Secondary end-points included maternal and neonatal complications.
In the two groups there were significant reductions in the glucose levels from baseline in both groups, however the inter
group difference between glibeclamide and insulin was not
significant, (Table 1).
Furthermore, there were no significant differences between the
glibenclamide and insulin groups in all safety parameters for
secondary end point, (Table 2).
The cord-serum insulin concentrations were similar in the two
groups, and glibenclamide was not detected in the cord serum
of any infant in the glibenclamide group.
The authors of the study concluded that in women with gestational diabetes, glibenclamide is a clinically effective alternative
to insulin therapy.12
Table 1. Primary Endpoint
GlibenclamideInsulin
Pretreatment
During treatment
Pretreatment
During treatment
114±19
105±16
116±22
105±18
The mean (±SD) blood
glucose concentration
(mg/dL)
(P=0.99)
Table 2. Secondary Endpoint
Safety parameterGlibenclamideInsulin
The percentage of infants who were large for gestational age
12%
13%
Incidence of macrosomia, defined as a birth weight of 4000 g or more
7%
4%
Lung complications
8%
6%
Neonatal hypoglycemia
9%
6%
Number admitted to neonatal intensive care unit
6%
7%
Incidence of fetal anomalies
2%
2%
Conclusion:
Insulin therapy is effective in achieving the appropriate levels
of glycemic control, but it is inconvenient and expensive.
Oral hypoglycemic agents are more convenient, improve the
adherence and are cheaper alternatives.
Among oral hypoglycemic agents it was found that: while
metformin, rosiglitazone, and most sulfonylureas cross the
placenta, glibenclamide on the other hand has been shown to
cross very little. Furthermore glibenclamide was found to be as
clinically effective and safe as insulin in glycemic control during
the second and third trimesters in a large and well designed RCT.
Further studies are needed to confirm the role of metformin and
thiazolidinedione in the management of gestational diabetes.
References:
1. Moretti, M.E., M. Rezvani, and G. Koren, Safety of Glibenclamide for Gestational
Diabetes: A Meta-Analysis of Pregnancy Outcomes. Ann Pharmacother, 2008.
42(4): p. 483-490.
2. Feig, D.S., G.G. Briggs, and G. Koren, Oral Antidiabetic Agents in Pregnancy and
Lactation: A Paradigm Shift? Ann Pharmacother, 2007. 41(7): p. 1174-1180.
3. Elliott, B.D., et al., Comparative placental transport of oral hypoglycemic agents
in humans: a model of human placental drug transfer. American Journal Of
Obstetrics And Gynecology, 1994. 171(3): p. 653-660.
4. Kraemer, J., et al., Perfusion studies of glibenclamide transfer across the human
placenta: implications for fetal safety. American Journal Of Obstetrics And
Gynecology, 2006. 195(1): p. 270-274.
7. Chan, L.Y.-S., J.H.-k. Yeung, and T.K. Lau, Placental transfer of rosiglitazone in the
first trimester of human pregnancy. Fertility and Sterility, 2005. 83(4): p. 955-958.
8. Towner, D., et al., Congenital malformations in pregnancies complicated by
NIDDM. Diabetes Care, 1995. 18(11): p. 1446-1451.
9. Glueck, C.J., et al., Pregnancy outcomes among women with polycystic
ovary syndrome treated with metformin. Hum. Reprod., 2002. 17(11): p.
2858-2864.
10.Jakubowicz, D.J., et al., Effects of Metformin on Early Pregnancy Loss in the
Polycystic Ovary Syndrome. J Clin Endocrinol Metab, 2002. 87(2): p. 524529.
5. Vanky, E., et al., Placental passage of metformin in women with polycystic ovary
syndrome. Fertility and Sterility, 2005. 83(5): p. 1575-1578.
11. Nicholas, A.C., et al., Improvement in insulin sensitivity followed by ovulation
and pregnancy in a woman with polycystic ovary syndrome who was treated with
rosiglitazone. Fertility and Sterility, 2001. 76(5): p. 1057-1059.
6. Charles, B., et al., Population Pharmacokinetics of Metformin in Late Pregnancy.
Therapeutic Drug Monitoring, 2006. 28(1): p. 67-72.
12.Langer, O., et al., A Comparison of Glibenclamide and Insulin in Women with
Gestational Diabetes Mellitus. N Engl J Med, 2000. 343(16): p. 1134-1138.
Toxi-Drug Info - Sept. 2009 - Volume 3 - Issue 3
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Minimizing adverse drug events
in elderly
Introduction:
A
dverse drug events (AEs) in the elderly are of great
concern in healthcare today because of a combination of
ageing populations and the tendency to prescribe for every
disorder experienced by patients. These AEs do not only
have a direct impact on patients in the form of loss of trust,
morbidity and mortality but also on healthcare professionals
in the form of stress and they pose an enormous financial
burden on society.
This may be due in part to the fact that most common chronic
diseases are prevalent in the elderly, but the wide spread use
of drugs such as diuretics, CNS agents and non steroidal
anti-inflammatory drugs, suggest that excess prescribing is a
continuing problem.2
Drug utilization data shows that the elderly are major drug
consumers, which suggests that over prescribing is common in
elderly.1 One study conducted in the United Kingdom showed
that elderly over 65 comprise 12%-18% of the population;
receive up to 40% of all prescriptions. The study also showed
that almost two-thirds of elderly may be taking either prescribed
or over the counter preparations at any one time.
1. Exaggerated physiological effects of drugs due to age related pharmacokinetics changes e.g. reduced renal and hepatic
clearance.
2. Co-morbidity resulting in the possibility of drug-disease interactions.
3. Poly-pharmacy drug-drug interactions.
4. Patient non-adherence possibly due to frailty, reduced dexterity and memory problems.3
The elderly (i.e. those aged 65 or older) are at
increased risk of ARs due to the following reasons:
Due to excessive prescribing or over-use of medicines by the
elderly, they experience a disproportionate share of unwanted
and unexpected adverse drug events. In a study published in the
US, it was reported that about one in three older persons taking
at least five medications will experience an adverse drug event
each year, and about two thirds of these patients will require
medical attention.4 Approximately 95 percent of these reactions
are predictable, and about 28% are preventable.5
Epidemiological studies showed that there are certain drug
classes most commonly associated with adverse drug events in
elderly, including: diuretics, beta-blockers, warfarin, selective
serotonin reuptake inhibitors, angiotensin-converting enzyme
(ACE)-inhibitors and non-steroidal anti-inflammatory drugs
(NSAIDs).
These treatments are frequently co-prescribed in this population,
thereby greatly increasing the risk.3
Remember
Ask your patients to bring all their
medications including prescription only,
over the counter (OTC), herbal and
homeopathic remedies at every visit.
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Toxi-Drug Info - Sept. 2009 - Volume 3 - Issue 3
PHARMACOVIGILANC
E
Table 1 Practical advice for clinicians when prescribing for elderly6
Recommendation
Examples
Advantages
Maximize the dose of one agent for
a specific disease before adding a
second agent
Anti-hypertensive and anti-diabetic agents
Less confusion and cost,
less risk of severe drug
reactions
Use one agent to treat two conditions:
reduce poly-pharmacy
Drugs used to treat hypertension and benign prostatic
hyperplasia, hypertension and angina
Less confusion and cost,
less risk of adverse events
Use an agent no more than once or
twice daily
Antihypertensive agents, such as ACE inhibitors,
calcium channel blockers, beta blockers
Better compliance
Avoid misuse of drugs: potentially
inappropriate drugs
Amiodarone, barbiturates (except Phenobarbital),
methyldopa, nifedipine
Less risk of adverse events
Minimize the use of anticholinergic
agents and discontinue when possible
Phenothiazine
major
tranquilizers,
atypical
antipsychotics, narcotics, antispasmodics, sedating
cold and cough medications, OTC sleep drugs, muscle
relaxants.
Less risk of adverse events
Ask patient to bring medications and
review at every visit
All medications including OTC drugs.
Less
confusion
compliance
Avoid overdosing of medications
Renal functions play an important role in altering
the effect of a drug in elderly. Use Cockcroft-Gault
equation in the absence of the 24 hrs urine measurement
to calculate age adjusted estimate of the glomerular
filtration rate.6
Less risk of adverse events
Avoid underuse of medications
Under-prescribing: rheumatoid arthritis beginning in
older adulthood, depression, diastolic heart failure and
ataxia secondary to normal pressure, hydrocephalus
are examples of conditions that should be diagnosed
and treated in older patients but are often missed.
Encourage patient adherence
Consider switching to combination medications or
once daily dosing to improve adherence, being careful
to balance improved convenience with increased
cost. Combine cognitive aids and patient education to
improve adherence such as tablet dispenser boxes.
Conclusions
Potentially preventable medication-related adverse events have
received increasing attention, in particular those, which are the
result of medical errors. The elderly are at elevated risk due to
physiological decline, co-morbidity and poly-pharmacy, resulting in particularly high rates of hospital admissions and death due
to potentially preventable medication-related adverse events.
Physicians have to find ways to streamline the medical regimen, such as periodically reviewing all medications and
avoiding new prescriptions to counteract adverse drug reactions. The use of drug interaction program or computerized
alerts is very beneficial to reduce medication errors and adverse drug reactions.3
better
Patient compliance
References:
1. Cartwright A, Smith C. Elderly people, their medicine and their doctors. London:
Routledge, 1988;39-76.
2. Prescribing in the elderly. Ken Woodhouse. J Hong Kong Med Assoc Vol. 43, No.
4, Dec. 1991; 205-208
3. Kathrin M. Cresswell, Bernard Fernando, Brian McKinstry and Aziz Sheikh.
Adverse drug events in the elderly. British Medical Bulletin 2007 83(1):259-274
4. Hanlon JT, Schmader KE, Koronkowski MJ, Weinberger M, Landsman PB, Samsa
GP, et al. Adverse drug events in high risk older outpatients. J Am Geriatr Soc
1997;45:945-8.
5. Gurwitz JH, Field TS, Harrold LR, Rothschild J, Debellis K, Seger AC, et al.
Incidence and preventability of adverse drug events among older persons in the
ambulatory setting. JAMA 2003;289:1107-16.
6. Drug therapy in elderly patients: how to avoid adverse effects and interactions.
http://www.consultative.com/display/article/10162/40114 Accessed on May 17 2009
7. Cockcroft-Gault equation, http://www.nephron.com/cgi-bin/CGSI.cgi. Accessed on
May 17 2009.
Toxi-Drug Info - Sept. 2009 - Volume 3 - Issue 3
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12
ELECTRONIC PRESCRIBING:
Benefits versus Risks
At A Glance:
1. PLANNING PHASE:
lectronic prescribing (e-Prescribing) is the utilization of
electronic systems to facilitate and enhance the communication of a prescription of medicine order, aiding the choice,
administration and supply of a medicine through knowledge
and decision support and providing a robust audit trails for the
entire medicines use process.
Prior to drafting an e-Prescribing strategy, all potential benefits
versus risks need to be considered. Later, the weight of each
identified barrier has to be tied (practically) in to an effective
solution prior to implementation. This workout can be summarized in 3 steps:
E
e-Prescribing has been heralded as bringing major benefits to patients by reducing the incidence of medications errors and improving communication about medicines.1 It will also support clinical
activity by interacting with knowledge sources and providing decision support at the point of prescribing or administration.
On the other hand, e-Prescribing is a critical component in the
overall strategy to enhance health care quality. By delivering clear
and accurate information throughout the prescribing process, ePrescribing can help reduce the estimated 3 million preventable
adverse drug events and reduce the estimated 7,000 deaths from
medication error that occur each year in the US.2
In consequence, e-Prescribing will impact on and require the
support of everyone who prescribes, supplies or administers
medicine. In addition to doctors and hospital pharmacists, this
will include nurses, midwives, and allied health professionals
such as radiographers and physiotherapists. Many other employees will also have an interest in the implementation of ePrescribing - from senior management teams within a health
care facility (HCF) to the information technology teams which
will provide local support to the systems.
PHASES OF E-PRESCRIBING IMPLEMENTATION:
The implementation of e-prescribing will require new roles in
health/pharmacy informatics to support the continued development of systems based on feedback. There will be changes to
practice and evidence generated that will enhance medicines
management, risk reduction, patient safety and quality improvement in a variety of ways. The systems will facilitate the
supply of medicines through links to stock control and automation. Time released from “traditional” activities will need to be
redirected to clinical activities and used to promote optimized
treatment for individual patients. Illustrated below, are the different phases of implementing e-Prescribing.
STEP 1: Identifying Benefits of Implementing e-Prescribing:
Literature revealed 3 categories of possible benefits:
1.1. Operational Benefits
l Prescription always available at point of need and at
multiple sites, saving staff time.2
2
l Facilitate compliance with policies and formulary.
l Accurate record of all drugs administered
l Ability to target clinical pharmacist activity to patients
with greatest need.
l Ability to quickly identify high risk patients
l Reduce transcription errors prescriptions
l Allergy warnings always available and linked to drug selection
l Reduce adverse drug events
l Identifies drug-drug interactions at the point of prescribing
1.2. Managerial Benefits
2
l Promote rational use of medicines.
l No legibility issues
2
l Information on drug availability at the point of prescribing.
l Notes can be attached clarifying decisions
l Reduce drug selection errors and ability to retrieve previous medication history for re-admissions.3
3
l Reduce dose, frequency and duration errors.
l Reduce risk of administration errors through bar code
recognition at point of administration.3
l Reduced delays in treatment by reducing delays from
prescribing to supply
l Reduce missed doses as prescription available at all times
l Ability to track and audit changes in drug treatment during admission
l Potential to link with other decision support systems e.g.
pathology that influence choice of drug, dose etc at the
point of prescribing.4
l Ability to restrict the prescribing of high risk drugs to
specific clinicians.4
l Accurate medication histories able to be transmitted to
GPs including changes to therapy.4
1.3. Financial Benefits
l Ability to accurately cost drug treatment of patients
down to what has been administered rather than what
has been supplied.4
l Ability to accurately track drugs excluded from insurance plan- for recharge purposes.
l Reduced cost of dealing with adverse drug events.
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REVIEW
Save staff time looking for and accessing drug charts by
medical, nursing and pharmacy staff.
l Save staff time transporting drug charts around the site
e.g. ward to pharmacy.
l Potentially some drug expenditure savings through tighter control of prescribing.2
l
STEP 2: Identifying risks of implementing e-Prescribing
2.1.Operational Risks
l Service delivery if system fails
l Does not cover all prescribing e.g. chemotherapy
l Incomplete use of system and therefore records if access
is not optimized, requires access to appropriate IT hardware e.g. laptops, tablets, mobile PCs, etc.5
No.
Barrier
2.2. Managerial Risks
l Need for manual backup system and procedures
l Staff deskilled in the use of hard copy
2.3.Financial Risks
5
l Initial capital outlay including the provision of portable units.
l Revenue costs for license
l Staff to support the system
STEP 3: Adjusting e-claim strategy to accommodate identified barriers and risks of implementation: Prior to implementation, we need to customize e-Prescribing strategy to
surmount the identified barriers practically. The table below
summarizes possible strategy remodeling to accommodate
latent barriers.
Strategy
1
Unclear goals for e-Prescribing
conversion
Identify clear measurable goals to be achieved through e-Prescribing
2
Magnitude of change overwhelms the
targeted HCPs/HCFs*
Consider phased implementation (e.g.: implement e-Prescribing for refills
first, follow with addition of e-Prescribing for new prescriptions , or implement e-prescribing to inpatient then to outpatient , tertiary then to PHC..etc)
3
HCPs/HCFs may lack technical skills
to implement e-Prescribing
Survey HCPs/HCFs to confirm mastery of basic computer/typing/change
management skills
4
Confusion as to how to integrate
e-Prescribing into current work flow
Conduct workflow analysis of current prescribing workflow including time
study
5
HCPs/HCFs anxiety regarding change
process or even job security
Appoint an in-house project manager. Engage staffs who perform prescription management activities to help document workflows. Clearly communicate benefits of e-Prescribing to the practice.
6
Lack of XYZ contribution
Appoint representatives from XYZ to be involved in choosing, implementing
and evaluating e-Prescribing system
7
E-Prescribing system does not
support critical percentage of patient
population
Make sure the e-Prescribing system chosen is compatible with majority of
participating payers
8
Learning curve for new system underestimated
Maintain flexible implementation timeline. Use vendor’s experience for
training/implementation learning curve estimate
9
New system does not perform on
“Day One”
Test software including pharmacy interface prior to go-live. Take typical day
prescription volume and do a dry run in a test database. Ask vendor if any
bugs exist in current release – if so ask about dates for patches or upgrades
10
Hardware does not operate correctly
Test all hardware in advance of go-live. Make sure staff/physicians are
familiar with operation of any new devices
11
Inadequate time and resources for
training.
Allow adequate time for training outside of clinical work sessions. Appoint
“super users” to assist staff and physicians. Assess team readiness prior to
committing to go-live date
12
HCPs/HCFs unprepared to fully
utilize new system
Schedule go-live soon after training. Consider short-term reduction of patient volume. Make sure “super users” are available. Confirm availability of
vendor support services
13
New process is not fully implemented
Monitor outcome measures and share with HCPs/HCFs. Ask for feedback
and quickly address problems as they are identified. Offer follow-up training
sessions. Confirm vendor support of training/ upgrades/ service support
* Note: HCPs/HCFs refer to that the strategy aims to cover
References:
1. The Institute of Medicine(US). To Err is human: building a safer health system.
National Academy Press 1999
2. Hillestad R et al. Can Electronic Medical Record Systems Transform Health Care?
Potential Health Benefits, Savings, and Costs, Health Affairs, 2005; 24(5):11031117.
3. Institute of Medicine, Preventing Medication Errors, National Academies Press,
Washington, DC, 2006.
4. Fischer, et. al., “Effect of Electronic Prescribing With Formulary Decision Support
on Medication Use and Cost,”Archives of Internal Medicine, 168 (22), 2008, pages
2433-2439.
5. E-Prescribing’s Impact on Cost and Quality: Implications for Pay-for-Performance
Initiatives. Presentation by Leo Barbaro, Vice President, Anthem BCBS Connecticut, Health Information Technology Summit, March 2005. McMullin ST, Lonergan
TP, Rynearson CS, et al. Impact of an evidenced-based computerized decision
Toxi-Drug Info - Sept. 2009 - Volume 3 - Issue 3
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Insulin Glargine (LANTUS®)
& Cancer - A Closer Look
Background
O
n Friday, June 26, 2009, the EASD (European Association
for the Study of Diabetes) released on its website and in its
journal ‘Diabetologia’ a series of papers, an editorial, a press release, a video statement, and patient information, all concerning
a “possible link between insulin glargine and cancer” based on
four observational studies and a randomized controlled trial.1
Other international organizations quickly followed by releasing
their own position statements. The American Diabetes Association advised patients using insulin not to stop taking it based
on the findings of the studies.2 The American Association of
Clinical Endocrinologists (AACE) did not recommend that the
use of any insulin be changed.3 The Endocrine Society and The
Hormone Foundation, the public education affiliate of The Endocrine Society, recommended that patients continue with their
current insulin therapy until they have discussed with their physicians the reasons why a particular insulin treatment was prescribed.4 Regulatory agencies also released position statements.
The FDA and Health Canada recommended that patients should
not stop taking their insulin therapy without consulting a physician, since uncontrolled blood sugar levels can have both immediate and long-term serious adverse effects.5,6 EMEA, on
the other hand, stated that the available data did not provide a
cause for concern and that changes to the prescribing advice
were therefore not necessary. 7
The World Health Organization (WHO) estimates that more
than 180 million people worldwide have diabetes.8 They also
state that the number is likely to more than double by the year
2030.8 In light of these statistics, it was no surprise that the
recent warnings about insulin glargine (LANTUS®) raised such
a global uproar.
Literature Review
1. According to the authors of the editorial, Insulin Glargine and
Cancer – An Unsubstantiated Allegation, none of the studies
showed a relationship between insulin glargine and cancer. 1
2. The German study found that there is a decrease in both
cancer risk and all-cause mortality when insulin glargine is
compared to human insulin; 1,9
3. The Swedish study found no increase in overall cancer risk
with insulin glargine, but for breast cancer there was an increased risk with use of insulin glargine alone, but not in
combination with other insulins, and with a decrease in allcause mortality; 1,10
4. The Scottish study found no increase in overall cancer risk
with insulin glargine and uninterpretable data with regard to
breast cancer; 1,11
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Toxi-Drug Info - Sept. 2009 - Volume 3 - Issue 3
5. The UK THIN study found no increase in overall cancer risk and no increase in breast cancer risk with insulin
glargine but did find an increase in risk with insulin and
insulin secretagogues versus metformin; 1,12
6. A small randomized study found no increase in cancer risk.1
A strength of this trial was that it was randomized (thereby
eliminating distribution bias); however, its shortfall was
that it was small.1
Discussion
Since none of the studies showed a relationship between insulin glargine and cancer, why were some patients advised to see
their healthcare providers anyway? The answer to this question
may not be as simple. It may be because individual study data
are not fully understood or expert agencies are in the process of
reviewing the data or, perhaps, the data collectively has simply
shaken confidence in a product once considered to be very safe
and effective – leaving experts confused.
The most likely answer may be a combination of reasons. This
is why a call for trial data to examine if a risk actually exists
has been resonating from every corner. A randomized trial may
be the best way to establish or refute whether a relationship
between insulin glargine and cancer exists.1 Currently, discussions are ongoing between FDA and the manufacturer of insulin glargine as to whether any additional studies evaluating the
safety and efficacy of this drug will need to be performed.
A large randomized trial has been underway since 2003, the ORIGIN (Outcome Reduction with an Initial Glargine Intervention)
trial.1 Examination of the frequency of cancer in ORIGIN may
help resolve the question; does insulin glargine have a similar
(or decreased) rate of cancer in comparison to the control group.1
However, if there is an increased rate of cancer in the insulin
glargine group, it will be impossible to distinguish whether that
increase is due to insulin use or insulin glargine use.1 Moreover,
given the observation that metformin use may result in decreased
cancer risk, the use of metformin may complicate analysis and
make interpretation difficult.1 In other words, if metformin was
used only in the standard therapy group, then a reduction in
cancer risk in that group when compared to the control therapy
group might have shown a false statistical increase in cancer risk
in the control therapy group. If both control and standard therapy
groups received metformin, then even if a cancer risk existed,
sensitivity analysis might not detect a difference.
Scenario in UAE
In UAE, approximately 19.5% of the population has either type
I or type II diabetes,8 a higher incidence rate when compared
to the rest of the developed countries. In addition, according to
Medication Safety
the WHO, incidence of diabetes and obesity are on the increase
in the UAE.8 Obesity and type II diabetes by themselves are
associated with an increased risk of cancer.1
2. The American Diabetes Association Website. http://www.diabetes.org/for-media/
pr-glargine-0602609.jsp. Accessed date: October 1, 2009.
Differences between the UAE population and individuals in the
studies published in Diabetologia and in the small randomized
trial do exist. Other differences such as sedentary lifestyle,
which is a major risk factor for diabetes, is a related factor that
may be worth considering when trying to extrapolate the data
to the UAE population.
4. The Endocrine Society Website. http://www.endo-society.org/advocacy/policy/
upload/Statement-for-Patients-on-Insulin-Glargine.pdf. Accessed date: October 1,
2009.
Would statistical power, clinical significance, number needed
to harm be any different if the study subjects were taken from
the UAE population? A weakness of the Scottish study (which
is acknowledged by the authors) was allocation bias; thereby,
those patients who were less healthy were treated with insulin
glargine.1,11 The average age of the patients in the German
study was 69.5 years.1 Would allocation bias be eliminated in
a population that was prescribed insulin glargine for a wider
age group and during all stages of the disease? In other words,
would replacing the subjects in the observational studies and
randomized trial with different subjects (without any other
changes to the designs) simply correct several of the limitations
of the studies? For the time being, we simply do not have the
answer to this and others questions.
3. The American Association of Clinical Endocrinologists (AACE) Website. http://
www.aace.com/. Accessed date: October 1, 2009.
5. Food and Drug Administration. www.fda.gov. Accessed date: September 15,
2009.
6. Health Canada. www.healthcanada.com. Accessed date: September 15, 2009.
7. European Medicines Agency. http://www.emea.europa.eu/. Accessed date:
September 15, 2009.
8. World Health Organization. http://www.who.int/mediacentre/factsheets/fs312/en/.
Accessed date: August 20, 2009.
9. Hemkens LG, Grouven U, Bender R, Gu¨ nster C, Gutschmidt S, Selke GW, Sawicki
PT: Risk of malignancies in patients with diabetes treated with human insulin or insulin
analogues: a cohort study. Diabetologia 2009; doi 10.1007= s00125-009-1418-4.
10. Jonasson JM, Ljung R, Talba¨ck M, Haglund B, Gudbjo¨ rnsdo` ttir S, Steineck G:
Insulin glargine use and short-term incidence of malignancies—a population-based
follow-up study in Sweden. Diabetologia 2009; doi 10.1007=s00125- 009-1444-2.
11. SDRN Epidemiology Group: Use of insulin glargine and cancer incidence in
Scotland: a study from the Scottish Diabetes Research Network Epidemiology
Group. Diabetologia 2009; doi 10.1007=s00125-009-1447-z.
12. Currie CJ, Poole CD, Gale EAM: The influence of glucose lowering therapies on
cancer risk in type 2 diabetes. Diabetologia 2009; doi 10.1007=s00125-009-1440–6.
13. Health Authority Abu Dhabi (HAAD). Circular No. PHM/29/09. July 22, 2009.
Conclusion
Toxicology Quiz
The data implicating insulin glargine as a cause of cancer was
inconclusive in the studies mentioned. However, this does not
mean that an increased risk does not exist - particularly in the
UAE population. Therefore, HAAD will continue to monitor
the situation closely for any new developments and alert the
public and healthcare professionals as necessary.
1.Of the 3,000 known species of snakes in the world,
approximately what percent are venomous?
HAAD Position Statement 13
The HAAD position is that treating physicians should carefully
investigate their patients before prescribing LANTUS® (insulin
glargine) and to report any adverse events to the HAAD Pharmacovigilance Center.
References:
1. Satish K. Garg, M.D.,1 Irl B. Hirsch, M.D.,2 and Jay S. Skyler, M.D., M.A.C.P.
Insulin Glargine and Cancer—An Unsubstantiated Allegation. DIABETES
TECHNOLOGY & THERAPEUTICS Volume 11, Number 8, 2009.
l
33 %
2.Intoxication by what element has been implicated
in the pathogenesis of “Alzheimer’a disease”?
l
Aluminum
l
Lead
l
Mercury
3.In treating an overdose of paracetamol, an antidote called N- ACETYLCYSTEINE (NAC) is commonly used. In order to be most effective, this antidote should be given before how many hours post
exposure have passed?
l
4 hours
l
8 hours
l
12 hours
3. 12 hours
European Medicines Agency’s Committee for Medicinal
Products for Human Use (EMEA - CHMP) state that the
available data does not provide a cause for concern and that
changes to the prescribing advice are therefore not necessary.
25 %
2. Aluminum
EMEA Position Statement
7
l
Answers : 1. 10 %
The FDA and Health Canada recommend that patients should
not stop taking their insulin therapy without consulting a
physician, since uncontrolled blood sugar levels can have both
immediate and long-term serious adverse effects.
10 %
Toxi-Drug Info - Sept. 2009 - Volume 3 - Issue 3
I
FDA and Health Canada Position
Statement 5,6
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16
Rumors Versus Truth
I’ve heard .... Sometimes facts get mis-stated ... statistics
misquoted ... or efficacy exaggerated.
If you’re hearing or seeing something .... that leaves you
wondering if it’s really true, tell us about it.
We’ll check it out for you and put the “best” Rumors here ...
along with the truth.
RUMOR
Combining Ibuprofen and Guaifenesin
can cause heart attacks in kids.
TRUTH: Websites and email inboxes are flooded with
claims of an 8 year-old girl dying after taking this combination.
Reassure patients that this is just an Internet rumor. There is
NO evidence it ever occurred...no confirming news reports,
additional details, or ANY verifiable stories of the event and
no serious interactions are expected between any drugs in this
combination …ibuprofen, guaifenesin, dextromethorphan, etc.
Tell people that problems due to OTC cough and cold products
in children are usually due to misuse or accidental ingestion. If
parents ask, tell them it’s safe to use Ibuprofen and guaifenesin
together and there is no evidence of interaction.
Reference:
1. Rumor vs Truth. Pharmacists Letter. http://www.pharmacistsletter.com- password
web access. Accessed on August 25,2009
RUMOR
Vitamin E interacts with statins
TRUTH: Lots of patients take vitamin E and other antioxidants with the hope of preventing heart disease.
There is some evidence that a high DIETARY intake of vitamin
E might reduce the risk of heart disease. But the most recent
evidence shows that vitamin E SUPPLEMENTS do not help
prevent primary or secondary heart disease or cardiovascular
events such as heart attack or stroke.2
Recent evidence suggests that taking a combination of antioxidants including vitamin E might actually be harmful. Many
patients with heart disease get a statin such as simvastatin, lovastatin, atorvastatin, etc. In addition to lowering the bad LDL
cholesterol, statins also increase the good HDL cholesterol.
Patients who take simvastatin and niacin in combination with
an antioxidant including vitamin E, vitamin C, selenium, and
beta - carotene seem to have LESS of the good HDL cholesterol.3 The antioxidant combination seems to decrease HDL by
about 15%.
Even though vitamin E plus other antioxidants might interact
with statins and decrease HDL levels, it’s too soon to say how
clinically significant this might be. And there’s evidence that
taking just vitamin E with a pravastatin has no adverse effect on
HDL.4
17
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Toxi-Drug Info - Sept. 2009 - Volume 3 - Issue 3
US TR
S
R
E
V
RUMORS
UTH
For now, think of this potential interaction as another reason to
think twice about recommending vitamin E for heart disease.
References:
1. Rumor vs Truth. Pharmacists Letter. http://www.pharmacistsletter.com- password
web access. Accessed on August 25,2009
2. Lonn E, Yusuf S, Dzavik V, et al. Effects of ramipril and vitamin E on
atherosclerosis: the study to evaluate carotid ultrasound changes in patients treated
with ramipril and vitamin E (SECURE). Circulation 2001;103:919-25.
3. Brown BG, Zhao XQ, Chait A. Simvastatin and niacin, antioxidant vitamins, or the
combination for the prevention of coronary disease. N Engl J Med 2001;345:1583-93.
4. Carlsson CM, Papcke-Benson K, Carnes M, et al. Health-related quality of life
and long-term therapy with pravastatin and tocopherol (vitamin E) in older adults.
Drugs Aging 2002;19:793-805.
RUMOR
Artificial food additives make kids hyperactive.
TRUTH: The belief that artificial food additives might be related
to hyperactive behavior in children stems from over 30 years ago.
A pediatric allergist by the name of Benjamin Feingold
proposed that synthetic flavorings and colors in the diet might
be a cause of hyperactivity, and proposed an elimination
diet. Many parents who have followed the “Feingold Diet”
have reported improvement in their children’s behavior.2 But
evidence for a link is conflicting. Until now, most research
showed no or little effect of additives on behavior.3
Now a well-designed study suggests that artificial food colorings
and benzoate preservative commonly found in sweets and
beverages can increase hyperactivity in kids with and without
attention deficit hyperactivity disorder (ADHD).4
But experts disagree on whether the increase in hyperactive
behavior is significant for most children. There are still
questions on who is most susceptible and whether genetics
might contribute. Plus it’s not clear whether the preservative or
a particular food coloring might be the cause.5
Tell parents with “hyperactive” children that limiting additives
in their child’s diet MIGHT help. But advise them that for most
children, the gains are likely to be small. If they really suspect
their child’s hyperactive behavior is out of the normal, refer
them to their pediatrician for evaluation.
References:
1. Rumor vs Truth. Pharmacists Letter. http://www.pharmacistsletter.com- password
web access. Accessed on August 25,2009
2. Wolraich ML and others. Effects of diets high in sucrose or aspartame on the
behavior and cognitive performance of children. N Engl J Med 1994;330:301.
3. McCann D, Barrett A, Cooper A, et al. Food additives and hyperactive behaviour
in 3-year-old and 8/9-year-old children in the community: a randomised, doubleblinded, placebo-controlled trial. Lancet 2007;370:1560.
4. Bateman B, Warner JO, Hutchinson E, et al. The effects of a double blind, placebo
controlled, artificial food colourings and benzoate preservative challenge on
hyperactivity in a general population sample of preschool children. Arch Dis Child
2004;89:506.
5. Schab DW, Trinh NT. Do artificial food colours promote hyperactivity in children
with hyperactive syndromes? A meta-analysis of double-blind placebo-controlled
trials. J Dev Behav Pediatr 2004;25:423.
FORMULARY UPDATE
Formulary Additions - New Medications
Drug Name
Dosage
Approved HAAD Indications
Comments
Pegaspargase
750 units/mL, 5 mL
vial
• Acute lymphoid leukemia, First-line, in combination with other agents
• Acute lymphoid leukemia, In combination with
other agents in patients with hypersensitivity to
L-asparaginase
Insulin
Glulisine
100 units / ml prefilled
pens & vials
• Diabetes mellitus type 1
• Diabetes mellitus type 2
Telmisartan
40 & 80 mg tablets
• Hypertension
Oseltamivir
75 mg capsule
• Influenza, Viruses Types A and B; Treatment
• Influenza, Viruses Types A and B; Prophylaxis
Zanamivir
5 mg diskhaler
• Influenza, Viruses Types A and B; Treatment
• Influenza, Viruses Types A and B; Prophylaxis
Restricted to FDA
approved indication in
Acute lymphoid leukemia
New dose
Amlodipine
10 mg tablet
New Dosage form
Insulin Biphasic Aspart 30/70
Insulin Glarigine
100 units/ml, 3 ml prefilled pen
100 units/ml, 3 ml cartridge
Formulary Deletions
Drug Name
Dosage
AQUA 40% /PARAFFINUM
Cream
AQUA 50% /PETROLATUM
Cream
AQUA 55%/CERAMIDE
Cream
AQUA 60% /GLYCERIN
Cream
AQUA 60% /PETROLATUM
Cream
AQUA 80% /BUTYLENE GLYCOL
Cream
TACHYDRITE & CARNALITE MINERALS
Maintainer Cream
TACHYDRITE & CARNALITE MINERALS
Body Lotion
TACHYDRITE & CARNALITE MINERALS
Initiator Lotion
TACHYDRITE & CARNALITE MINERALSs
Scalp Gel
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