Scientific Information update
Editorial
This is the second issue of the bulletin for the year 2006. Several topical issues that are of current
relevance and importance are hereby brought to our readers attention .We certainly hoped that
the information covered has been magnificently useful particularly to the health professionals
and the public in general.
This edition is brought to you with usual format:
The scientific information update column reviews topics on treatment, prevention
and clinical manifestations of Cryptococcosis among HIV- infected people as well
as other pertinent issues like Antibiotics for surgial prophylaxis
The regulatory tips column concentrates on the Inclusion of New Drug in to the NDL
Among other Current issues, Antimalarial Drug Resistance and Artemisinin-based
combination therapy is being stated briefly on its own column.
News updates on recent activities of the authority are sorted out in its very own column
A self-assessment test is being presented on its usual column for our readers active
participation in the line of duty. Readers are kindly requested to send attempted
answers. Answers will be posted on the next issue.
Last of all, we, the editors, take this opportunity to invite our readers to provide their feedback
and suggestions regarding the bulletin so that we can make this more useful. You are welcome to
write and send us drug and therapeutics related articles for our bulletin. We value them a lot.
Cryptococcosis
Epidemiology
Cryptococcosis is the most common lifethreatening AIDS related fungal infection,
and the second most common overall (after Candida). Five to 10% of people with
1
Scientific Information update
AIDS (PWAs) develop cryptococcosis,
Cryptococcosis among patients with AIDS
with two thirds of them developing cryp-
most commonly occurs as a subacute men-
tococcal meningitis (CM), in which the
ingitis or meningoencephalitis with fever,
organism infects the meninges, the fluid-
malaise, and headache. Classic meningeal
filled membranes lining the brain, includ-
symptoms and signs (e.g., neck stiffness or
ing the spinal fluid (cerebrospinal fluid or
photophobia) occur in approximately one
CSF). Cryptococcal pneumonia is com-
fourth to one third of patients. Certain pa-
mon among people with chemotherapy or
tients might present with encephalopathic
organ-transplant-related immunosuppres-
symptoms (e.g., lethargy, altered menta-
sion, but not among people with AIDS.
tion, personality changes, and memory
Among PWAs, CM is most common
loss). Analysis of the CSF usually indi-
among those with fewer than 50, most of-
cates a mildly elevated serum protein,
ten fewer than 25, CD4 cells. Cryptococ-
normal or slightly low glucose, and a few
cosis decreased as a cause of death among
lymphocytes and numerous organisms.
PWAs from 7.7% to 5.0% between 1987-
The opening pressure in the CSF is elevat-
1993, probably due to improved antifungal
ed (with pressures >200 mm of water) in
treatment and prophylaxis.
up to 75% of patients. Disseminated dis-
Cryptococcal infections occur much less
frequently among HIV-infected children
(1%) than adults. Infection primarily occurs among HIV-infected children aged 6–
12 years and most frequently in those with
ease is a common manifestation, with or
without concurrent meningitis. Approximately half of patients with disseminated
disease have evidence of pulmonary rather
than meningeal involvement. Symptoms
and signs of pulmonary infection include
cough or dyspnea and abnormal chest ra-
CD4+ cell counts indicating severe immunosuppression.
diographs. Skin lesions might be observed.
Diagnosis: Clinical and lumbar puncture
with CSF analysis including Indian ink
Clinical Manifestations
staining, CSF cryptococcal antigen, and
fungal culture.
Treatment
2
Scientific Information update
Preventing Recurrence
tered lifelong suppressive treatment (i.e.,
Patients who have completed initial thera-
secondary prophylaxis or chronic mainte-
py for cryptococcosis should be adminis-
Amphotericin B-- Produced from a strain of Streptomyces nodosus. Antifungal activity of
amphotericin B results from its ability to insert itself into fungal cytoplasmic membrane at
sites containing ergosterol or other sterols. Aggregates of amphotericin B accumulate at
sterol sites, resulting in an increase in cytoplasmic membrane permeability to monovalent
ions (eg, potassium, sodium). At low concentrations, the main effect is increased intracellular loss of potassium, resulting in reversible fungistatic activity; however, at higher concentrations, pores of 40-105 nm in cytoplasmic membrane are produced, leading to large lossDrug Name
es of ions and other molecules. A second effect of amphotericin B is its ability to cause auto-oxidation of the cytoplasmic membrane and release of lethal free radicals. Main fungiFlucytosine
:- of
Although
the exact
mode
of action
is unknown,
is proposed
to
cidal activity
amphotericin
B may
reside
in ability
to causeflucytosine
auto-oxidation
of cell memactbranes.
directly on fungal organisms by competitive inhibition of purine and pyrimidine uptake
and
indirectly
intracellularby
metabolism
where it
is converted
5-fluorouracil
If therapy
is by
supplemented
oral flucytosine,
therapy
can be to
used
until patientafter
is a penfebrile
etrating
fungal
cells.
Inhibits
RNA
and
protein
synthesis.
Active
against
Candida
and
and alert and spinal fluid cultures are negative for 6 wk; then, patient can be placed on fluDrug Name
Cryptococcus
conazole. species and generally used in combination with amphotericin B.
Use in combination with another agent because acquired resistance develops frequently
when flucytosine is administered alone.
Well absorbed
orally butdeoxycholate
should be administered
IV to patients IV
who are critically ill.
Adult Dose
AmphotericinB
0.7 mg/kg-1.0mg/kg/day
100-150 mg/kg/d PO divided qid
Adult Dose
100 mg/kg/d PO or 25-37.5 mg/kg PO q6h as supplement to amphotericin B therapy
Contraindications Documented hypersensitivity
Antineoplastic agents may enhance potential of amphotericin B for renal toxicity, bronPediatric Dose
50-100 mg/kg/d PO divided qid
Interactions
chospasm, and
hypotension;
corticosteroids,
digitalis, and
thiazides that
mayselectively
potentiate hypokaFluconazole
:-Synthetic
oral antifungal
(broad-spectrum
bistriazole)
inhiblemia;
risk
of
renal
toxicity
is
increased
with
cyclosporine
fungal cytochrome
P-450 and sterol C-14 alpha-demethylation, which prevents converContraindications its
Documented
hypersensitivity
sion of lanosterol to ergosterol, thereby disrupting cellular membranes. Has little affinity
Interactions
Amphotericin B may increase toxicity of flucytosine; cytosine may inactivate flucytosine
forCmammalian
which is has
believed
to explain
its low toxicity. Available as tab
Pregnancy
- Safety for cytochromes,
use during pregnancy
not been
established.
Drug
Name
Pregnancy
C -oral
Safety
for use duringaspregnancy
not been
for
administration,
a powder has
for oral
susp,established.
and as a sterile solution for IV use. Has
Precautions
Caution
in renal
bone
marrow
dose
impairment
fewer
adverse
effects
andsuppression;
better electrolytes
tissueadjust
distribution
than
older
systemic
imidazoles.
Monitor
function,
serum
suchinasrenal
magnesium
and potassium,
liverDOC
funcfortion,
long-term
prophylaxis.
CBC, and hemoglobin concentrations; resume therapy at lowest level (eg, 0.25
mg/kg) when therapy is interrupted for more than 7 days; hypoxemia, acute dyspnea, and
Precautions
interstitial infiltrates may occur in patients with neutropenia who receive leukocyte transfusions
(separate
of then
amphotericin
infusion
time of leukocyte transfusion); fever
Adult Dose
400
mg PO
qd for time
10 wk;
100-200 mg
PO qdfrom
for life
and chills are not uncommon after first few administrations of drug; rare acute reactions
Pediatric Dose
2-3may
mg/kg
PO qd
include
hypotension, bronchospasm, arrhythmias, and shock
Contraindications Documented hypersensitivity
Levels may increase with hydrochlorothiazides; fluconazole levels may decrease with longterm coadministration of rifampin; may increase concentrations of theophylline, phenytoin,
Interactions
tolbutamide, cyclosporine, glyburide, and glipizide; effects of anticoagulants may increase
with fluconazole coadministration
Pregnancy
C - Safety for use during pregnancy has not been established.
Adjust dose for renal insufficiency; closely monitor if rashes develop, and discontinue drug
3 failure
if lesions progress; may cause clinical hepatitis, cholestasis, and fulminant hepatic
(including death) when taken with underlying medical conditions (eg, AIDS, malignancy)
Precautions
or while taking multiple concomitant medications; not recommended for breastfeeding
Scientific Information update
nance therapy), unless immune reconstitu-
exposure. No reports exist about its use in
tion occurs as a consequence of HAART
the first trimester of pregnancy in humans.
(see the following recommendation).
Flucytosine might be metabolized to 5fluoruracil. It should be used in pregnancy
Discontinuing Secondary Prophylaxis
only if clearly indicated.
(Chronic Maintenance Therapy). Apparently, adult and adolescent patients are
at low risk for recurrence of cryptococcosis when they have successfully completed a course of initial therapy for cryptococcosis, remain asymptomatic with regard to signs and symptoms of cryptococcosis, and have a sustained increase (e.g.,
Special prescriber's points
Amphotericin
>6 months) in their CD4+ T lymphocyte

counts
nary cryptoccocal , amphotericin B is
to
>100-200
cells/µL
after
HAART.
In non-AIDS-related extrapulmu-
continued
for
longer
period
(4-8
weeks),as the goal of therapy is cure ra-
Restarting Secondary Prophylaxis.
ther
than long-term suppression
Maintenance therapy should be reinitiated
if the CD4+ T lymphocyte count decreases

to 100-200 cells/µL.
nal or preferably intraventricular admin-
Intrathecal therapy (lumbar, cister-
istration through an Ommaya reservoir)
Special Considerations During Pregnancy
may be considered in severe unrespond-
Diagnosis and treatment for cryptococ-
with IV administration. Corticosteroids
cosis among HIV-1–infected pregnant
are commonly given simultaneously to
women are the same as for nonpregnant
reduce local reaction.
ing fungal meningitis, in conjunction
women. Amphotericin B should be used in
the first trimester to avoid the potential for

teratogenicity with fluconazole or itracon-
tion, potassium and magnesium is indi-
azole.
Frequent monitoring of renal func-
cated in all patients
Flucytosine is teratogenic in rats at high

doses, but not at doses similar to human
hours). Infusion over 24 hours has been
IV infusion should be slow (over 4
4
Scientific Information update
shown to be safer, but there are no con-
ride or a bacteriostatic agent can cause
vincing efficacy data for constant infu-
precipitation. Owing to a wide range of
sion. Because amphotericin B act in
incompatibilities, it is advisable not to
concentration-dependent fashion, con-
mix amphotericin with any other agent
stant infusion may be sub-optimal
or to administer it simultaneously via
the same IV line.

Adverse effects due to IV admin-
istration may be minimized by premedication with corticosteroid or antipyretics
Fluconazole

Liver function test should be monitored as clinically indicated

Amphotericin B should be reconsti-
tuted with the recommended diluents

Maximum rate of infusion, 200
mg/hour
only; solution containing sodium chlo-
5
Scientific Information update
6
Scientific Information update
Antibiotics for surgical prophylaxis
Summary
Surgical antibiotic prophylaxis is defined as
Surgical antibiotic prophylaxis is defined as
the use of antibiotics to prevent infections at
the use of antibiotics to prevent infections at
the surgical site. Prophylaxis has become the
the surgical site. It must be clearly distin-
standard of care for contaminated and clean-
guished from pre-emptive use of antibiotics
contaminated surgery and for surgery in-
to treat early infection, for example perfo-
volving insertion of artificial devices. The
rated appendix, even though infection may
antibiotic selected should only cover the
not be clinically apparent.
likely pathogens. It should be given at the
correct time. For most parenteral antibiotics
this is usually on induction of anaesthesia. A
single dose of antibiotic is usually sufficient
if the duration of surgery is four hours or
less. Inappropriate use of antibiotics for surgical prophylaxis increases both cost and the
selective pressure favouring the emergence
of resistant bacteria.
The original surgical antibiotic prophylaxis
experiments were performed 40 years ago in
pigs. The results concluded that 'the most
effective period for prophylaxis begins the
moment bacteria gain access to the tissues
and is over in three hours'. Since then there
have been many studies in animal models
and in humans undergoing surgery. This has
resulted in the principles of antibiotic
Introduction
prophylaxis becoming an accepted part of
surgical practice.
Wound infections are the commonest hospital-acquired infections in surgical patients.
Approximately 30-50% of antibiotic use in
They result in increased antibiotic usage,
hospital practice is now for surgical prophy-
increased costs and prolonged hospitaliza-
laxis. However, between 30% and 90% of
tion. Appropriate antibiotic prophylaxis can
this prophylaxis is inappropriate. Most
reduce the risk of postoperative wound in-
commonly, the antibiotic is either given at
fections, but additional antibiotic use also
the wrong time or continued for too long.
increases the selective pressure favoring the
Controversy remains as to duration of
emergence of antimicrobial resistance. Judi-
prophylaxis and also as to which specific
cious use of antibiotics in the hospital envi-
surgical procedures should receive prophy-
ronment is therefore essential.
laxis.
7
Scientific Information update
Principles of surgical antibiotic prophylaxis

Decide if prophylaxis is appropriate

Determine the bacterial flora most likely to cause postoperative infection (not every species needs to be covered)

Choose an antibiotic, based on the steps above, with the narrowest antibacterial
spectrum required

Choose the less expensive drug if two drugs are otherwise of equal antibacterial
spectrum, efficacy, toxicity, and ease of administration

Administer dose at the right time

Administer antibiotics for a short period (one dose if surgery of four hours duration or less)

Avoid antibiotics likely to be of use in the treatment of serious sepsis

Do not use antibiotic prophylaxis to overcome poor surgical technique
Indications for surgical antibiotic
prophylaxis
Widely accepted indications for antibiotic
A classification system which ranks proce-
prophylaxis are contaminated and clean-
dures according to their potential risk for
contaminated surgery and operations involv-
infectious complications has greatly facili-
ing insertion of an artificial device or pros-
tated the study of surgical antibiotic prophy-
thetic material. Less well-accepted indica-
laxis. This system ranks procedures as:
tions for prophylaxis include clean opera-

Clean
tions in patients with impaired host defences

Clean-contaminated
or patients in whom the consequences of

Contaminated.
infection may be catastrophic, for example
neurosurgery, open heart surgery and ophthalmic surgery.
8
Scientific Information update
Choice of antibiotic
The choice of the antibiotic for prophylaxis
surgical prophylaxis comprise a large por-
is based on several factors. Always ask the
tion of hospital pharmacy budgets.
patient about a prior history of antibiotic
Commonly used surgical prophylactic anti-
allergy, as beta-lactams are the commonest
biotics include:
type of antibiotics used in prophylaxis. A

history of severe penicillin allergy (anaphy-
Intravenous
'first
generation'
cephalosporins - cephazolin
laxis, angioedema) means that cephalospor-

Intravenous gentamicin
ins are also contraindicated, as there is a

Intravenous or rectal metronidzole
small but significant risk of cross-reaction.
Most importantly, the antibiotic should be
active against the bacteria most likely to
cause an infection. Most postoperative infec-
(if anaerobic infection is likely)

Oral tinidazole (if anaerobic infection is likely)

Intravenous flucloxacillin (if methi-
tions are due to the patient's own bacterial
cillin-susceptible staphylococcal in-
flora. Prophylaxis does not need to cover all
fection is likely)
bacterial species found in the patient's flora,

Intravenous vancomycin (if methi-
as some species are either not particularly
cillin-resistant staphylococcal infec-
pathogenic or are low in numbers or both.
tion is likely).
Parenteral 'second generation' cephalospor-
It is important to select an antibiotic with the
ins such as cefotetan have improved anaero-
narrowest antibacterial spectrum required,
bic and aerobic Gram-negative cover com-
reducing the emergence of multi-resistant
pared to first generation cephalosporins.
pathogens and also because broad-spectrum
They are sometimes used as a more conven-
antibiotics may be required later if the pa-
ient, but more expensive, alternative to the
tient develops serious sepsis. The use of
combination of metronidazole plus either
'third generation' cephalosporins such as
first generation cephalosporin or gentamicin
ceftriaxone and cefotaxime should therefore
for abdominal surgical prophylaxis.
be avoided in surgical prophylaxis. Often
several antibiotics are equal in terms of anti-
The bacterial flora in some hospitalised pa-
bacterial spectrum, efficacy, toxicity, and
tients may include multi-resistant bacteria
ease of administration. If so, the least expen-
such as methicillin-resistant staphylococci.
sive drug should be chosen, as antibiotics for
An assessment then needs to be made for
each surgical procedure about whether or
9
Scientific Information update
not prophylaxis with parenteral vancomycin
Oral or rectal antibiotics need to be given
is indicated. Unnecessary use of vancomycin
earlier to ensure adequate tissue concentra-
selects for vancomycin-resistant enterococci
tions during surgery. Metronidazole sup-
(VRE),vancomycin-intermediate Staphylo-
positories are commonly used in bowel sur-
coccus aureus (VISA), and vancomycin-
gery and must be given 2-4 hours before it
resistant Staphylococcus aureus (VRSA).
begins. Topical antibiotics are not recommended, with the exceptions of ophthalmic
Route and timing of antibiotic ad-
or burns surgery.
ministration
Duration of antibiotic administration
It is critical to ask the patient about betalactam allergy prior to anaesthesia to mini-
Persistence of tissue concentrations past the
mise the risk of anaphylaxis under anaesthe-
period of surgery and recovery of normal
sia. A test dose of antibiotic is not necessary
physiology following anaesthesia does not
before surgery if the patient denies antibiotic
improve efficacy and increases toxicity and
allergy.
cost. If the operation lasts four hours or less,
one antibiotic dose is usually sufficient. In
Prophylactic antibiotics are usually given
prolonged surgery of greater than four
intravenously as a bolus on induction of an-
hours, further antibiotic doses may be re-
aesthesia to ensure adequate tissue concen-
quired to maintain the concentration, partic-
trations at the time of surgical incision. This
ularly if the antibiotic has a short half-life.
timing of dosing is particularly important for
Continuing antibiotic prophylaxis until sur-
most beta-lactams which have relatively
gical drains have been removed is illogical
short half-lives. Vancomycin has to be in-
and also of unproven benefit.
fused over one hour so it must be started
earlier so the infusion finishes just before
Conclusion
induction.
Surgical antibiotic prophylaxis is an effecIntramuscular antibiotics are less commonly
tive management strategy for reducing post-
used than intravenous antibiotics. They are
operative infections, provided that appropri-
typically given at the time of pre-medication
ate antibiotics are given at the correct time
so that peak tissue levels are attained at the
for appropriate durations and for appropriate
most critical time, the time of surgical inci-
surgical procedures. In most cases, surgical
sion.
antibiotic prophylaxis is given as a single
intravenous dose as soon as the patient is
10
Scientific Information update
stabilised under anaesthetic, prior to skin
as both the cost of individual antibiotics and
incision. It is important to use a narrow
the endemicity of multi-resistant bacteria in
spectrum antibiotic appropriate to the site of
certain units or hospitals are subject to fre-
surgery. Hospital surgical antibiotic prophy-
quent change.
laxis protocols should be regularly reviewed,
11
Scientific Information update
Complementary medicine
Ginger-Not just a spice
such as (6)-, (8)-, and (9,10)- shogaol, (6)Ginger is used worldwide as a cooking
and (10)- dehydrogingerdione, (6)- and (10)-
spice, condiment and herbal remedy. The
gingerdione, zingerone, and zingibain. Some
Chinese have used ginger at least 2500 years
as a digestive aid and antinausea remedy and
of the clinically established therapeutic uses
to treat bleeding disorders and rheumatism.
of ginger are discussed below.
It was also used to treat baldness, toothache,
snakebite, and respiratory conditions.In Tra-
Post operative nausea and vomiting:
ditional Chinese Medicine (TCM), ginger is
The effect of powdered ginger root was
considered a pungent, dry, warming, yang
compared with metoclopramide and place-
herb to be used for ailments triggered by
bo. In a prospective, randomized, double-
cold, damp weather. Ginger is used exten-
blind trial the incidence of prospective nau-
sively in Ayurveda, the traditional medicine
sea and vomiting was measured in 120
of India, to block excessive clotting, reduce
women presenting for elective laparoscopic
cholesterol and fight arthritis. In Malaysia
gynaecological surgery on a day stay basis.
and Indonesia, ginger soup is given to new
The incidence of nausea and vomiting was
mothers for 30 days after their delivery to
similar in patients given metoclopramide
help warm them and to sweat out impurities.
and ginger (27% and 21%) and less than
In Arabian medicine, ginger is considered an
those who received placebo (41%). The re-
aphrodisiac.
quirement for postoperative antiemetics was
lower in those patients receiving ginger. The
Ginger’s medicinal components are derived
requirements for postoperative analgesia,
from the rhizome or root of the plant Z. of-
recovery time and time till discharge were
ficinale. Its pungent properties also contrib-
the same in all groups. There was no differ-
ute to its pharmacologic activities. Ginger
ence, in the incidence of possible side ef-
contains cardiotonic compounds known as
fects such as sedation, abnormal movement,
gingerols, volatile oils, and other com-
itch and visual disturbance between the three
pounds,
groups. Zingiber officinale is an effective
and
promising
prophylactic
antiemetic,
which may be especially useful for day case
surgery.
12
Scientific Information update
toms of seasickness, ginger appeared to re-
Effects on platelet aggregation: In 20
duce the severity of sea sickness (measured
healthy young male volunteers, ginger sup-
as score 0-9) rather than reducing the num-
plementation (5 gms daily) significantly in-
ber of subjects who reported symptoms.
hibited the platelet aggregation induced by
ADP (adenosine diphosphate) and epineph-
Knee osteoarthritis: A 6-week trial with
rine . In human volunteers who took a huge
261 subjects which used 255 mg per day of
(10 gram) one-time dose of dried ginger,
a patented ginger extract, (EV. EXT 77) re-
there was a marked inhibition of platelet
ported effectiveness similar in magnitude to
aggregability.
that reported with NSAIDs. Apart from the
above mentioned indications, ginger is also
Motion
sickness:
Ginger’s
efficacy
used in variety of conditions with varying
against motion sickness was tested in a dou-
success. It is known to have cardiotonic,
ble-blind, randomized study involving 80
antilipemic, carminative, antiulcer, hypogly-
healthy naval cadets who were unaccus-
cemic, anti-inflammatory effects, antibacte-
tomed to sailing in heavy seas. The cadets
rial, antineoplastic and antioxidant proper-
took either 1 g of powdered ginger rhizome
ties. However the therapeutic effects of gin-
or 1g of placebo while sailing in heavy seas
ger in normal dietary doses are not known.
and maintained scorecards noting their
Further studies and larger trials on the thera-
symptoms every hour for the next four
peutic uses of ginger are warranted.
hours. In the 48 sailors who reported sympo-
Source: (quarterly publication of Drug Information Center, Manipal Teaching Hospital, Pokhara,
Nepal, Volume 3 issue 1,2005)
13
Scientific Information update
Adverse effects associated with antiretroviral therapy
associated with antiretroviral drugs are deIn recent years, excitement about the bene-
scribed below.
fits of combination anti-HIV therapy has
been tempered by a growing awareness of
Gastrointestinal Adverse Effects
the problems that accompany the use of anti-
The most common side effects associated
HIV drugs. In addition to drug resistance
with anti-HIV drugs are those that affect the
and the difficulty of adhering to complex
stomach and intestines. Both nucleoside ana-
regimens, side effects associated with highly
log and protease inhibitor drugs frequently
active antiretroviral therapy (HAART) have
cause gastrointestinal side effects. Typical
become a major concern.
gastrointestinal side effects include diarrhea,
nausea, vomiting, and abdominal cramps;
Common Types of Adverse Effects
intestinal
gas
(flatulence),
acid
reflux
Anti-HIV therapy affects the entire body,
("heartburn"), and constipation may also
and the various drugs may cause adverse
occur. Among the protease inhibitors,
reactions in almost all organs and systems.
nelfinavir is the most common cause of di-
This is not surprising, since the drugs often
arrhea, although diarrhea associated with
interfere with genetic and cellular processes
full-dose ritonavir tends to be more severe.
that are common to both viruses and human
Gastrointestinal side effects are not only
cells. However, certain classes of drugs are
unpleasant and detrimental to quality of life
more often associated with specific types of
but can also interfere with the absorption of
side effects; for example, some nucleoside
water, food, and medications, potentially
analogs are associated with low blood cell
leading to dehydration, disruptions in body
counts and mitochondrial toxicity, some
chemistry, malnutrition, weight loss, and
non-nucleoside reverse transcriptase inhibi-
inadequate drug levels.
tors (NNRTIs) are associated with skin reactions, and long-term treatment, especially
Several measures have proved helpful in
with regimens that include a protease inhibi-
managing gastrointestinal side effects. In
tor, is associated with increased blood fat
many cases, the body adjusts to medications
levels and body fat redistribution. Some of
with continued use, and symptoms subside
the most common types of adverse events
on their own. If a drug does not need to be
taken on an empty stomach, taking it with
14
Scientific Information update
food may help to reduce nausea and vomit-
edies. Mint and ginger can relieve nausea,
ing. A number of prescription antiemetic
and acidophilus capsules may help control
medications are available to help control
diarrhea. Marijuana and its synthetic deriva-
nausea, including ondansetron, lorazepam,
tive dronabinol have been shown to reduce
metoclopramide, and prochlorperazine; the
nausea and have the added benefit of stimu-
latter two drugs should be used cautiously
lating the appetite. For more information on
due to the risk of their own side effects, in-
managing nausea and diarrhea. With both
cluding movement disorders (tardive dyski-
vomiting and diarrhea, it is important to
nesia).
avoid dehydration and electrolyte imbalances. Balanced sports drinks such as Gatorade,
If the cause of diarrhea has been carefully
or a mixture of salt and sugar in water, can
evaluated and it is not related to an infection
help prevent both problems.
or another underlying condition (e.g., lactose
intolerance), over-the-counter drugs such as
Reporting adverse effects associated with
loperamide, attapulgite, or psyllium deriva-
HAART helps screen out safer drugs for use
tives (e.g., Metamucil), or stronger prescrip-
in the foreseeable future. Meet your moral as
tion drugs such as diphenoxylate or pan-
well as your professional commitment by
crelipase, may help keep it under control.
reporting any suspected adverse events
Calcium supplement tablets have been
against ARV drugs.
shown to alleviate diarrhea associated with
nelfinavir; however, people should consult
Adverse Drug Reaction Monitoring and
their physicians before taking supplemental
Promotion Control Division
calcium.
Planning, Drug Information Establish-
Dietary changes, such as eating several
ment and Distribution Department
small meals or snacks throughout the day
Drug Administration and Control Au-
and reducing consumption of fats, dairy
thority of Ethiopia
products, and spicy foods, may help control
A continuation of the text above with topics on adverse
nausea and diarrhea. Many people find al-
effects of ARV drugs on Central Nervous System will
be on our next bulletin issue.
ternative therapies beneficial, including acupuncture, wrist acupressure, and herbal rem-
15
Scientific Information update
Methadone (opioid) for Treatment of Opioid dependence and withdrawal
with individualized health care and medicalMethadone was synthesized during the Sec-
ly prescribe methadone to relieve with-
ond World War for use as a painkiller on the
battlefield by Germen Company I.G. Farben.
drawal symptoms, reduces the opiate cravMethadone is long acting (more than 24 hrs)
ing, and brings about a biochemical balance
drug from opioid class. Its pharmacological
in the body.
effect helps in preventing withdrawal, reducing drug hunger (craving) and in adequate
Evidence shows that continuous MMT is
amount, blocks the euphoric effect of heroin
associated with several other benefits
(to discontinue heroin use) and other opioid.

MMT costs about 13 dollar
per day and is considered a
For more than 30 years this synthetic narcot-
cost effective alternative to
ic has been used to treat opioid addiction. It
is a rigorously well-tested medication that is
safe and efficacious for treatment of narcotic
incarceration.

of 4:1, meaning 4-dollar eco-
withdrawal and dependence.
nomic benefit accrues for every 1 dollar spent on MMT
U.S. Federal regulation permit methadone to
be used in detoxification and maintenance
MMT has a benefit –cost ratio

MMT significantly decrease
treatment (MMT) programs for opioid ad-
the rate of HIV infection and
diction. Short- term (up to 30 day) and long
other diseases for the patients
term (up to 180 days) detoxification pro-
participating in MMT pro-
grams use methadone to alleviation adverse
grams.
physiological or psychological consequence
of withdrawal from illicit opioids, with the
dosage gradually achieved. After 180 days,
patients who have not achieved a drug free
state are considered to be receiving maintenance treatment. Many MMT patients require continuous treatment, sometimes over
a period of years. MMT provides the addicts
Research and clinical studies suggest that
long term MMT is medically safe. When
methadone is taken under medical supervision, long-term maintenance causes no adverse effects on heart, lungs, liver, kidneys,
bones, blood, brain, or other vital organs.
Methadone produces no serious side effects,
16
Scientific Information update
although some patient’s experiences minor
symptoms such as constipation, water retention, drowsiness, skin rash, excessive sweating, and changes in libido. Once methadone
dosage is adjusted and stabilized or tolerance increase, these symptoms usually subside.
Finally, if methadone treatment is helped
with other approaches like self-help groups
(e.g. Narcotic Anonymous), day treatment
and counseling, it may give much better result that methadone treatment alone.
17
Current issue
Antimalarial Drug Resistance
antimalarial drug concentrations are sufficient to inhibit multiplication of susceptible
Antimalarial drug resistance is the
ability of a parasite strain to survive
and/or multiply despite the administration and absorption of a drug
given in doses equal to or higher
than those usually recommended,
but within the limits of tolerance of
the subject.
Resistance to antimalarial drugs is proving
to be a challenging problem in malaria control in most parts of the world. Since early
60s the sensitivity of the parasites to chloroquine, the best and most widely used drug
parasites but are inadequate to inhibit the
mutants, a phenomenon known as "drug selection". This selection is thought to be enhanced by subtherapeutic plasma drug levels
and by a flat dose-response curve to the
drug.
The important factors that are associated
with resistance are: 1. Longer half-life. 2.
Single mutation for resistance. 3. Poor compliance 4. Host immunity. 5. Number of
people using these drugs.
for treating malaria, has been on the decline.
Newer antimalarials were discovered in an
The characteristics of a drug that make it
effort to tackle this problem, but all these
vulnerable to the development of resistance
drugs are either expensive or have undesira-
are: a long terminal elimination half-life, a
ble side effects. Moreover after a variable
shallow concentration-effect relationship,
length of time, the parasites, especially the
and mutations that confer marked reduction
falciparum species, have started showing
in susceptibility. There is now circumstantial
resistance to these drugs also.
evidence that the development of resistance
can be delayed by combining a well-
Resistance to antimalarial drugs arises as a
result of spontaneously occurring mutations
that affect the structure and activity at the
molecular level of the drug target in the ma-
matched drug pair, i.e. combining one drug
that rapidly reduces parasite biomass with a
partner drug that can remove any residual
parasites.
laria parasite or affect the access of the drug
to that target. Mutant parasites are selected if
18
Current issue
Resistance to chloroquine: Resistance began
Chloroquine
resistance
is
maintained
from 2 epicentres – Columbia (South Amer-
throughout the whole life cycle and is trans-
ica) and Thailand (South East Asia) in early
ferred to the progeny. Cross-resistance has
part of 1960s. Since then, resistance has
been demonstrated with other 4-amino quin-
been spreading worldwide and reached the
olines and mepacrine, but not to quinine,
Indian state of Assam in 1973. Resistance is
mefloquine, PABA blockers or antifolates.
conferred by a stable mutation, which is
transferred to the progeny. It involves multi-
Proguanil (PABA blocker) and py-
ple mutations which means that resistance
rimethamine (antifolate): These drugs
need not be complete - it may be partial also.
act by sequential inhibition of enzymes of
folate metabolism. Resistance to these drugs
Chloroquine acts by getting accumulated in
has developed over the past 30 years and is
the food vacuole where it inhibits heme pol-
now wide spread. Resistance develops very
ymerase. Resistant strains are able to efflux
rapidly and remains stable due to a single
the drug by an active pump mechanism and
point mutation. The mechanism of resistance
release the drug at least 40 times faster than
to these drugs involves modification of drug
sensitive strains, thereby rendering the drug
transport systems, increased synthesis of
ineffective. There is an increase in the sur-
blocked enzymes, increase in drug inactivat-
face area of the resistant parasites, permit-
ing enzymes and the use of alternative
ting more efficient pinocytosis. Binding of
pathways. Resistance is seen for vivax and
chloroquine with haemoglobin breakdown
falciparum. Hence these drugs may not be of
product to form toxic complexes is also pre-
any benefit in complicated malaria.
vented.
Resistance to quinine: Chloroquine reNonspecific pump inhibitors like calcium
sistance has brought this drug back to the
channel blockers or antagonists of calmodu-
limelight. Quinine remains quite effective
lin (e.g. verapamil), cyprohaptedine, chlor-
even after extensive use. Reports of re-
pheniramine and hydroxyzine have been
sistance to quinine are rare, but cases have
shown to suppress the efflux pump mecha-
been reported from Thailand and East Afri-
nism. But in practice these drugs have not
ca. High degree of resistance to quinine is
shown any benefit on reversing chloroquine
not common. For reasons not known clearly,
resistance and it is too early to say anything
it has been difficult to induce quinine re-
about the utility of these agents in the man-
sistance in experimental conditions. Efficacy
agement of chloroquine resistant P. falcipa-
of quinine can be increased by adding tetra-
rum malaria.
19
Current issue
cycline group of drugs. Poor compliance is
stable resistance has not been observed so
a major drawback of this drug.
far. But going by the trend so far the parasite
might acquire resistance to artemesinin also.
Resistance to mefloquine: Sporadic cases of mefloquine resistance have been re-
Prevention of drug resistance:
ported from Thailand and Kenya. Structural-
Resistance develops most rapidly when a
ly it is close to quinine and hence cross-
population of parasite encounters subthera-
resistance with quinine is common. Re-
peutic concentration of antimalarial drugs.
sistance develops when the parasite is able
The following points will be helpful in re-
to efflux the drug. Initially it was given at
ducing the emergence of resistance:
dose of 15mg/kg and was combined with
sulfadoxine/pyrimethamine to reduce emer-
1. Selection of drugs - Use conven-
gence of resistance. This approach did not
tional drugs first in uncomplicated
succeed in Thailand probably due to the al-
cases. Greater the exposure, higher
ready existing high-grade resistance to sul-
will be the emergence of resistance.
fa/pyrimethamine. Later the dose was increased to 25 mg/kg. Even at this dose effi-
2. Avoid drugs with longer half-life if
possible.
cacy of mefloquine is only 50% in Thailand.
3. Avoid basic antimalarials for non-
Since it is easy to induce resistance for mef-
malarial indications (e.g. Chloro-
loquine due to its prolonged half-life, its use
quine for rheumatoid arthritis in a
should be limited, especially since it has
malarial endemic area).
cross resistance to quinine. To prevent de-
4. Ensure compliance.
velopment of resistance to this valuable
5. Monitoring for resistance and early
drug, it has been suggested that mefloquine
treatment of these cases to prevent
should always be used in combination with
their spread.
another antimalarial, like pyrimethamine/
sulphadoxine.
6. Clear policy of using newer antimalarials.
7. Use of combinations to inhibit
Resistance to Artemisinin com-
emergence of resistance.
pounds:These are peroxide antimalarials
which release carbon centred free radicals
Source:(www.malariasite.com)
when they come in contact with heme. True
20
Current issue
Artemisinin-based combination therapy (current issue)
Rationale for use of artemisinin-
mission) thereby potentially reducing
based combination therapy
malaria transmission and particularly the
Artemisinin is the active antimalarial
transmission of resistant strains of ma-
component isolated from the medicinal
laria.
herb Artemisia annua, which has been
used for centuries in China as a tradi-
Artemisinin-based Combination
tional treatment for fever and malaria. In
Therapy
recent years, artemisinin derivatives
With the possible exception of artemis-
have become the focus of worldwide at-
inin derivatives, resistance of P falcipa-
tention in the light of emerging re-
rum to all available alternatives has been
sistance of Plasmodium falciparum to
frequently documented. Artemisinin de-
first line drugs; to date resistance to ar-
rivatives used alone are associated with
temisinin has not been demonstrated in
high treatment failure rates unless ad-
malaria parasites. While artemisinin de-
ministered for seven days, which is not
rivatives require at least seven days of
often achieved as symptoms are general-
treatment when administered alone,
ly relieved within two-three days. Thus,
when combined with other first-line
artemisinin derivatives should only be
drugs, artemisinin-based combination
used in combination with a second effec-
therapies (ACTs) can eradicate parasites
tive antimalarial; poor efficacy of this
quickly and protect against the develop-
component significantly compromises
ment of resistance to both drugs. Im-
the efficacy of the combination.
proved cure rates and decreased gametocyte carriage have been confirmed in
limited African field trials. Artemisinin
derivatives are the only first-line malaria
treatments to act on gametocytes (the
stage of the malaria parasite’s life cycle
responsible for ongoing malaria trans-
Although there are some minor differences in oral absorption and bioavailability between the different artemisinin
derivatives, there is no evidence that
these differences are clinically significant in current formulations. It is the
21
Current issue
properties of the partner medicine that
 artemether-lumefantrine,
determine the effectiveness and choice
 artesunate + amodiaquine,
of combination. ACTs with amodia-
 artesunate + mefloquine,
quine,
 artesunate + sulfadoxine–
atovaquone-proguanil,
chloro-
quine, clindamycin, doxycycline, lumefantrine,
mefloquine,
pyrimethamine.
piperaquine,
pyronaridine, proguanil-dapsone, sulfa-
Artemether-lumefantrine
doxine–pyrimethamine and tetracycline
This is currently available as co-
have all been evaluated in trials carried
formulated tablets containing 20 mg of
out across the malaria-affected regions
artemether and 120 mg of lumefantrine.
of the world. Some of these are studies
The total recommended treatment is a 6-
for product development.
dose regimen of artemether-lumefantrine
The following ACTs are currently rec-
twice a day for 3 days.
ommended :
Body weight in kg
(Age in years)
No. of tablets at approximate timing of dosing
0h
8h
24h
36h
48h
60h
5-14
(<3)
1
1
1
1
1
1
15-24
(3-8)
2
2
2
2
2
2
25-34
(9-14)
3
3
3
3
3
3
>34
(>14)
4
4
4
4
4
4
The regimen can be expressed more simply for ease of use at the programme level as follows: the second dose on the first
day should be given any time between 8 h and 12 h after the first dose. Dosage on the second and third days is twice a day
(morning and evening).
An advantage of this combination is that
dren of less than 10 kg is similar to that
lumefantrine is not available as a mono-
in
therapy and has never been used by itself
lumefantrine is now recommended for
for the treatment of malaria. Recent evi-
patients 5 kg. Lumefantrine absorption
dence indicates that the therapeutic re-
is enhanced by co-administration with
sponse and safety profile in young chil-
fat. Low blood levels, with resultant
older
children,
and
artemether-
22
Current issue
treatment failure, could potentially result
milk or fat-containing food – particularly
from inadequate fat intake, and so it is
on the second and third days of treat-
essential that patients or carers are in-
ment.
formed of the need to take this ACT with
References
1.
23
Regulatory Tips
Nevirapine and serious liver adverse reaction: implication for fixed dose combination
The symptom of nevirapine liver toxicity
Nevirapine belongs to the class of non-
may be misleading: a rash, a fever, or
nucleoside reverse transcriptase inhibitors (NNRTI's) and is one of the recommended drugs in the WHO first-line antiretroviral (ARV) regimens for the
treatment of adult and adolescent HIV
patients.
Nevirapine has been associated with severe liver toxicity in some cases. The
product label has been revised several
times over the last couple of years to include more information on liver toxicity
associated with long-term nevirapine
use; health care providers and patients
have been warned about the appropriate
use of ARV triple combination therapy
containing nevirapine.
flu-like symptoms. Any of these symptoms may be associated with elevated
liver enzymes. On the other hand, patients may be asymptomatic before the
onset of rapidly progressive liver failure
and death. Nevirapine liver toxicity typically occurs after only a few weeks of
dosing and may progress to liver failure
despite monitoring of laboratory test,
which is not characteristics of other antiretroviral drugs. Conversely, if patient
has not experienced liver toxicity within
the first 3-4 months of treatment with a
nevirapine-containing regimen, the risk
of subsequent liver toxicity is low.
Females and patients with higher CD4+
Liver Toxicity
Both clinically symptomatic liver toxicity are observed with the use of nevirapine , either as a single dose treatment to
reduce mother-to-child transmission or
in combination with other HIV drugs.
cell counts are at increased risk of liver
toxicity. Female have a three fold higher
risk of symptomatic nevirapine liver toxicity than males, and females with CD4+
cell counts > 250 cells/mm3 have a 12
fold risk of symptomatic liver toxicity
24
Regulatory Tips
than female with CD4+ cell count < 250.
childbearing potential or who are preg-
Males with CD4+ cell counts >400
nant.
cells/mm3 have a five fold higher risk of
symptomatic liver toxicity than male
Fixed dose combination (FDCs)
Nevirapine also available as a Fixed
with CD4+ cell counts< 400.
Nevirapine-related deaths due to symptomatic liver toxicity, including some in
HIV-infected pregnant women, have
been reported to the Food and Drug
Administration Medwatch programme in
the United States. Serious and fatal liver
toxicity have also been reported to the
World Health Organization (WHO) Adverse Drug Reaction database, Vigibase.
Dose Combination (FDC) with two other
drugs, lamivudine and stavudine. FDC
simplify treatment and drug management
issues, improve adherence of health-care
workers to treatment standards, decrease
errors in drug administration, simplify
drug forecasting, procurement, distribution and stocking because of fewer items
and lower volumes are necessary, and
reduce the risk of misuse of single drugs.
Globally, NNRTI- based regimens are
Due to these advantages the use of FDCs
the most widely prescribed combinations
is likely to increase, particularly in coun-
for initial therapy. In spite of the poten-
tries with limited health-system infra-
tial for serious and life-threatening liver
structures. However, since CD4 testing
toxicity and skin rash with nevirapine, it
facilities are not always available in
remains an important part of the HIV
these settings, there is a real danger of
treatment regimen for many HIV-
indiscriminate use of FDCs containing
infected individuals worldwide. It is a
nevirapine also in those individuals who
potent NNRTI with demonstrated clini-
may be at real risk for hepatotoxicity.
cal efficacy when administered in appropriate combination regimens. The
Conclusion
hepatotoxicity however, makes
it less
Health professionals responsible for the
suitable for treating patients who use
management of HIV-infected persons
other hepatotoxic drugs such as rifam-
are advised that significant liver toxicity
picin. On the other hand, nevirapine may
may develop if a nevirapine-containing
be the best choice in women of
regimen is initiated in-patient with rela-
25
Regulatory Tips
tively high CD4+ cell counts. This adverse effect is linked to the chemical
composition of the drug and hence, will
likely develop regardless of weather the
drug is formulated separately or as part
of a FDC. It remains important to improve laboratory testing facilities in locations where antiretroviral therapy is
distributed to identity and manage this
and other possible adverse effects.
References
1. Scaling up antiretroviral therapy
in
resource-limited
settings:
Treatment guideline for a public
health approach. Geneva, World
Health Organization, 2003
2. FDA Public Health Advisory for
nevirapine. United States Food
and Drug Administration, 19
January
2005
http://www.fda.gov/cder/drug
/advisory/nevirapine.htm)
3. http://www.boehringeringelheim.com/hiv/prod/
26
Regulatory Tips
New Drug Included in to the NDL
Since its establishment, the National Drug
many drugs were reviewed and approved for
Advisory Committee has conducted several
inclusion in to the drug list for human use and
regular meetings. Among many discussions on
for veterinary use as stated in table 1 and table
the meetings, evaluation of new drugs for in-
2 respectively.
clusion in to the National Drug List was one of
the main agenda.
On other hand table 3 indicates those drugs
reviewed by the committee and which are not
Clinical safety and efficacy data, pharmaco-
yet approved. Insufficient data on the safety
dynamic and pharmacokinetic summary, pre-
and efficacy of the drugs, absence of justifica-
caution and warnings, advantage over the ex-
tion on the advantage of the drug over the ex-
isting drugs and approval status of the drug in
isting drug in the list in terms of safety, effica-
other country’s were few of the elements to
cy, cost, ease on route of administration etc..
list that were reviewed during the screening of
were the reasons that the drugs were not in-
new drugs for inclusion in to the list. After the
cluded in the list. However, when such a defi-
committee reached on the final decision for
ciencies are submitted the committee will re-
inclusion of the drug in to the list the chairman
view the matters and give its recommenda-
will present the committees recommendations
tions for inclusion or request further justifica-
to the General Director of DACA. When such
tion.
recommendations made by the committee are
approved by the General Director, a circular
On this opportunity the Authority would like
official letter will be disseminated to all con-
to inform all professionals, institutions and
cerned body either for registration of the drugs
organizations to give us any comments regard-
or for information purpose. Accordingly,
ing on the list of drugs either for inclusion or
deletion.
27
Regulatory Tips
Table 1. List of Drugs included for human use
S/N
GENERIC NAME
1 Cefixime
DESCRIPTION
200mg,400 tablet
TGROUP
Aniti-infective, Other Antibacterials
2 Neomycin+Polymyxin+Nystatin
35,000+35,000iu+100,000 vaginal Gynacological medication
Tablet
3 Captopril+Hydrochlorthiazide
50mg+25mg tablet
Antihypertensive
4 Diclofenac sodium+Misoprostol
50mg+200mcg tablet
Antirheumatics(NSAID+PGE)
5 Ofloxacin
200mg/100ml injection,Tablet
Aniti-infective, Other Antibacte200mg,400mg
rials
6 Mefloquine
250MG tablet
Anti-infective,Anti-malarial
7 Cefprozil
125mg/5ml,250mg/5ml oral solu- Aniti-infective, Other Antibactetion
rials
8 Lamuvidine+Nevirapine+Stavudine 150mg+200mg+30mg/40mg tablet Antiretroviral
9 Paracetamol
1g injection
Analgesic
10 Terbenafine
1% cream
Antifungals
11 Calcium carbonate
350mg,500mg,700mgTablet
Antacids
12 Iron gluconate + Manganese glu5mg+1.33mg+0.77mg,Oral solu- Antianemic agent
conate+Copper gluconat
tion
13 Levonorgestrel
0.75mg tablet
Emergency contraceptive
14 Fosinopril
10,20mg tablet
Antihypertensive, ACE inhibitors
15 Mifepristone and Misoprostol
200mcg and 200mcg tablet
Regimen for therapeutic abortion
16 Glimepride
1,2,4mg tablet
Oral Hypoglycemic
17 Budesonide+Formoterol fumarate
80/4.5mcg/dose and
Bronchodialator/Antiasthmatics
160/4.5mcg/dose aerosol
18 Salmeterol+Fluticasone
50/100,50/250,50/500 per dosel
Bronchodialator/Antiasthmatic
19 Esomeprazole
20mg capsule,f/c tablet
Antiulcer
20 Mometasone furaote
0.05% intransal spray
Anti-inflamatories, topical
21 Pseudoephedrine+Loratadine
120mg+5mg tablet
Non-sedating antiallergic/decongestant
22 Ezetimbe
10mg tablet
Antilipemic
23 Anastrazole
1mg film coated tablet
Antineoplastic
24 Artemether+Lumfantrine
20mg+120mg Tablet
Anti-infective,Anti-malarial
25 Enoxaparine
20mg/0.2ml,40mg/0.4ml,60mg/0.6 Anticoagulant
ml,80mg/0.8ml,100mg/ml
26 Artesunate
100mg,200mg Tablet
Anti-infective, Anti-malarial
27 Zinc phosphate
20mg dispersible tablet
Minerals
28 Mebendazole
500mg tablet
Anthelmintic
29 Tribenoside+Lignocaine
400mg+40mg Suppository
Antihaemorroidal
30 Acetylsalicylic acid
81mg tablet
Antirheumatic
31 AmphotericinB
Lozenges
Anti-infective
32 Magnesium hydroxide+Aluminium Oral suspension
Antacid/Antiflatulent
Hydroxide+Simeticone
28
Regulatory Tips
S/N
GENERIC NAME
33 Pholcodine
34 Alfuzocin
35 Drotaverine
36 Zolpidem
37 Carbocisteine
38 Tadalafil
39 Insulin(rDNA origin produced in
E.coli)
40 Atomexitine
41
42
43
44
45
46
47
48
49
Duloxetin
Olanzapine
Bevacizumab
Trastuzumab
Ibandronate
Rituximab
Granisetron Hydrochloride
Capecitabine
Amphotericin B
50 Clindamycine phosphate
51 Artemether
DESCRIPTION
TGROUP
0.06%,0.12% syrup
Dry cough suppresant
2.5mg,5mg,10mg,Tablet
Benign Prostatic hyperplasia
40mg Tablet
Antispasmodic
10mg Tablet
Hypnotic
Carbocisteine2%,5% syrup
Mucolytic
10mg tablet
Drugs for Erectile dysfuncition
Insulin lispro, Insulin
Antidiabetic
lispro/protamine 50/50,and 25/75%
suspension
5mg,10mg,18mg,25mg,40mg,60m Drugs for Attention defig capsule
cit/Hyperactivity disorder
30mg,40mg,60mg
Antideprresants
5mg tablet
Anticonvulsant
25mg/ml vial
Antineoplastic
440mg/vial injection
Antineoplastic
50mg tablet
Antineoplastic
100mg/10ml vial
Antineoplastic
2mg Tablet
Antineoplastic
Tablet
Antineoplastic
Liposomal injection 50mg in 15ml Anti-infective,Drugs for Leishand 30ml vial
maniasis
1% topical solution
Anti-infective,Antiacne drug
40mg Suppository, 40mg/.
Anti-infective,Anti-malarial
5ml,80mg/ml oral suspension
A forum to discuss an initiative to contain an antimicrobial resistant in Ethiopia
29
The extent of supply and use of antimicrobials drugs is very high compared to drugs for
pia, which was held on March 2,2006,at Hil-
other diseases. Sustaining the proper supply
ton hotel Addis Ababa.
management and use of these drugs is essential for ensuring the provision of quality services in the country. In relation to this, different responsible bodies including health
The objective of the meeting was to promote
containment of antimicrobial resistant in
Ethiopia and to discuss the potential to implement the initiative in our country.
proffetionals, training institutions, and policy makers have an indispensable role in pre-
Participants from government agencies, aca-
venting the emergence and spreading of re-
demic and research institutions, donors and
sistant to these drugs.
international agencies attended the meeting.
Finally, the meeting was ended up by
Taking this in to considerations, Drug Administration and Control Authority in collaboration with MSH/RPM+ has organized a
achieving consensus on the proposed approach to contain an antimicrobial resistant
in Ethiopia and planning for next steps.
Luncheon meeting that discussed initiative
to contain antimicrobial resistant in Ethio-
Training /workshop on veterinary drug supply management and rational use
veterinary clinics, academic and research
In an effort to promote rational use of veter-
institutions.
inary drugs, Drug administration and control
authority has organized a training/ workshop
The trainees have been trained on the basic
on veterinary drug supply management and
principles of Rational use of drug and drug
rational use, which was conducted from
and drug supply management.
March 6-9, 2006,at Adama Ras Hotel, Adama. There were 27 participants in total from
The trainees have been trained on the basic
regional agricultural offices,
principles of Rational use of drug and drug
supply management. Besides the already
developed formulary and Standard Treatment Guidelines were familiarized.
The training-workshop was conducted in a
very participatory manner. A very thought-
30
ful and intensive discussion on the subjects
forwarded by the participants towards the
of interest was undertaken between the par-
presenters and response was given accord-
ticipants and presenters. Inquires requiring
ingly.
elaboration and in-depth explanation were
Rational Drug Use Indicator Study
The Drug Administration and Control Au-
For this purpose one Prescriber and one
thority is undertaking rational drug use indi-
pharmacy professional from each of the se-
cator study in 40 hospitals selected from all
lected health facilities were trained on data
regions and city administrations. This study
collection methods and related issues for
is part of the national integrated drug infor-
three days in two rounds from April 24-26
mation management system project.
and May 2-4, 2006 in Addis Ababa. In this
training pharmacist from regional health
The main objective of the study is to collect
bureaus and DACA staffs were also includ-
baseline information on the drug use prac-
ed to participate in the study as supervisors.
tices of the health institutions from available
facility data sets in order to obtain a clear
Data collection has been started on May 8,
picture of the problems hindering the ration-
2006. After all the collected data is received,
al use of drugs. Bases on this data various
it will be uploaded in the drug database, ana-
interventions will be planned and imple-
lyzed and the result will be shared with
mented by the relevant authorities and the
stakeholders.
impacts of the interventions will be assessed
after one year.
31
Tutorial
Tutorial
1. Surgical antibiotic prophylaxis for clean elective surgery started just before operation
should be continued for:
A.One day
B. Three days
C. Five days
D.Seven days
2. Trimethoprim (T) is combined with sulfamethoxazole (S) in a ratio of 1:5 to yield a
steady state plasma concentration ratio of:
A. (T) 1: (S) 5
B. (T) 1: (S) 10
C. (T) 1: (S) 20
D. (T) 5: (S) 1
3. Chloroquine resistance p.falciparum malaria can be cured by the following drugs
except:
A. Quinine
B. Pyrimethamine + sulfadoxine
C. Primaquine
D. artesunate
4. Which of the following drug is suitable for treatment of malaria during pregnancy
A. Quinine B. chloroquine C. pyrimethamine D. primaquine
5.which of the following is most likely to cause methadone witharawal whenthe two are
co-administered?
A.Kaletra B.ritonavir C.ddI D.Nevirapine E.nelfinavir
32