Epidemiological data show that the most inpatient disease in Iran resulting
in hospitalization is poisoning. In addition, drug poisoning is the second cause
of mortality in hospitalized patients in the country (Anonymous,
2008). For management of most of poisonings, at least one kind of antidote
should be used. Antidote is a natural or synthetic compound that interacts with
the action of toxin in the body. Until now, more than 30 antidotes in different
categories have been known in the world (http://inchem.org,
September 2009; Theakston et al., 2003; Abdollahi
et al., 2003).
Iran like other countries faces many cases of human drug overdose and poisoning
that need special poisoning care and existence of specific antidotes (Ghazinour
et al., 2009; Shadnia et al., 2007;
Moghadamnia and Abdollahi, 2002; Abdollahi
et al., 1997). As reported earlier, Iran has one of high-standard
drug registration policies in the region that one of its main objectives is
to afford essential drugs such as antidotes available for treatment and management
of diseases within the country (Nikfar et al., 2005)
and review of Iranian data would be a sample model for future studies specially
in neighbor countries.
Assessment of accessibility and utilization of antidotes has a great impact for plicy-makers because procurement of them is costly for government and it is very important to evaluate them in terms of availability, accessibility, affordability and their rationality of use.
There is no report on the use, availability and cost expenditure of antidotes in the country yet. Regarding the importance of this kind of information in health policy, we aimed to systematically review accessibility and affordability of antidotes in Iran during 2004-2008.
MATERIALS AND METHODS
Demographic and epidemiologic data about antidotes and their impacts in economic
situation of the country were extracted from Iranian drug affair's, drug selection
committee, pharmaceuticals statistics, direct interview with stockholders and
key opinion leaders in toxicology and World Health Organization (WHO) reports
access date: September 2009).
Data were extracted and analysed in 3 different manners including demographic, economic and health information, availability and accessibility of antidotes and 5 year cost-utilization trends.
For evaluation of availability, Iranian drug list was evaluated for existence of antidotes in the country. Information of registered drugs and their prices were collected from Iranian pharmaceutical regulatory affairs for evaluation of accessibility and affordability.
Demographic, economic and health information: Background information about demographic, economic and health contexts in 2006 have been summarized in Table 1. As shown in this Table 1, the population of Iran is more than 70,270,000 and the life expectancy for male and female are 69 and 73 years, respectively. Gross national income per capita in Iran is 9,800 USA dollar (USD).
Total expenditure on health per capita is 731 USD that is 7.8% of GDP (Gross Domestic Production) and total drug expenditure is 24000 billion Rials (10000 Rials≈1 USD). Data in this table show that probability of dying under age five is 35 per 1000 live births. Meanwhile probability of dying between age of 15 and 60 years for males and females were 170 and 106 per 1000 population, respectively.
|| Demographic, economic and health information in Iran
||Availability and accessibility of antidotes in Iranian drug
list and in the market
Availability and accessibility of antidotes: Table 2 shows the list of antidotes and their availability in IDL. In addition, the registered antidotes which are accessible in the market are shown in Table 2. As seen, different processes are needed to add a new drug to national drug list and for registration. Registration means that drug is accessible in the pharmacies. Ninety percent of all antidotes are available in IDL while 73% of them are registered and available in the market. Entire IDL includes 2230 medicines that 27 of them are antidote (1.1%).
Five year utilization trends of antidotes: Five-year utilization trends
of antidotes in Iran including the amount of use in each year and the price
of each antidote are shown in Table 3.
|| Five year utilization trends of antidotes in Iran
For all registered antidotes, the amount of accessibility in each year are
indicated during last five year from 2003 to 2008. Assessment of requirement
for each of them during different years as a trend of usage has been useful
for decision makers to better shape the health policy.
Regarding obtained results in terms of availability, IDL include most of antidotes.
It should be mentioned that special kind of official registration for pharmaceutical
products exists in Iran. Firstly, a committee accepts adding of a drug to IDL
and then to ensure its availability and then in case of demand to make them
accessible, other registration process is implemented. Results show that only
60% of antidotes of IDL have been registered and are accessible in the market.
The volume of utilization of existing antidotes during 5 years indicate that
25% of them are almost expensive (more than 40000 Rials or 10 dollars) that
is 1% of expenditure basket of Iran. All antidotes are under umbrella of insurance
while as an exception, there is a 90% extra subsidization for deferoxamine mesylate
as antidote for iron because of its use in thalasemic patients and also its
new indications in lung diseases (Mousavi et al.,
For better accessibility, almost all of these antidotes are available in the
referral poisoning hospitals which are specialized for toxicology services and
are covered by insurance services. In other words, eighty percent of the prices
of these antidotes are paid by the insurance companies to make them affordable.
As shown in Table 3, consumption of atropine sulfate 0.5
mg/1 mL ampoule in terms of volume is diminished during 5 years because of adding
atropine sulfate 20 mg/2 mL ampoule to IDL. Data indicate that the change in
dose of atropine not only reduced the total number of atropine 1 mL used but
saved nursery time and the package cost. This led to a kind of cost reduction
in terms of economics scale. Results also indicated that use of naloxone HCl
0.4 mg/1 mL ampoule has been reduced in the last 5 years which might be an evidence
for change of usage of the opioid narcotics or related products (Shadnia
et al., 2007). The use of amyl nitrite ampoule has been increased
more than 10 times comparing with the average use of this product during the
5 years. At the present, there seems no toxicological reason for use of this
antidote. Surprisingly the increased use of amyl nitrate is associated with
a reduced usage of sodium nitrate and sodium thiosulfate. The first thing that
comes to mind is that amyl nitrate is being abused for unknown purposes.
The total unit of protamine sulfate consumption has been decreased during last 3 years and this is compatible with the use of heparin during these years. Three years ago, low molecular weight heparins like enoxaparin sodium and dalteparin sodium were registered and entered to the Iranian market that has resulted in lower use of protamine sulfate.
In most of the countries, one of oximes (pralidoxime or obidoxime) has been
registered and is available for organophosphate poisonings (Rahimi
et al., 2006) but both of these antidotes are within IDL and available
in the market. Regarding higher price of obidoxime and its higher rate of side
effects in comparison to pralidoxime, it seems rational to exit one of them
from IDL. Results also indicate that despite of adding of intravenous ethanol
to IDL (Table 2), the real demand of this product is not clear
and therefore none of domestic manufacturers tried to produce or import it to
the Iranian market. The reason behind this defect returns to lack of information
or ineffective relationship between drug department of the government and the
importers or manufacturer companies and poisoning centers. As shown in Table
3 for polyvalan anti-botulism there was fixed amount of utilization during
last 5 years that is the outcome of special limitation rule of national regulatory
to restrict cosmetic use of this antidote.
Total medicines which were used in Iran during the year 2008 was 39.85 USD
per capita in terms of value and 439 per capita in terms of volume. The total
amount of antidotes that were used at the same period in terms of value was
0.05 USD per capita and in terms of volume was 0.2 per capita. Among a total
of 40000 physicians who are working in Iran, clinical toxicologists are estimated
30-50 working in only 10 hospitals in the country that have special poisoning
management services. Surprisingly, in spite of lack of adequate healthcare services
in clinical toxicology, epidemiological data show that the most inpatient diseases
in the country that result in hospitalization is poisoning and the poisoning
is the second most common cause of mortality in hospitalized patients (Anonymous,
Regarding multi-purpose usage of antidotes and lack of accurate data and information about poisoning, it is too hard to estimate the real demand for antidotes. Sometimes lack of adequate information about access to antidotes and sometimes high prices of them are barriers of good management of poisoning that result in defective strategic depot of the antidotes in the country. Effective impact of poisoning in economical and social concerns of the life necessitates implementation of stronger policies in clinical toxicology matters.
This study is the outcome of an in-house non-financially-supported study. Authors declare no conflict of interest.